Growth factor restriction impedes progression of wound healing following cataract surgery: identification of VEGF as a putative therapeutic target

Secondary visual loss occurs in millions of patients due to a wound-healing response, known as posterior capsule opacification (PCO), following cataract surgery. An intraocular lens (IOL) is implanted into residual lens tissue, known as the capsular bag, following cataract removal. Standard IOLs allow the anterior and posterior capsules to become physically connected. This places pressure on the IOL and improves contact with the underlying posterior capsule. New open bag IOL designs separate the anterior capsule and posterior capsules and further reduce PCO incidence. It is hypothesised that this results from reduced cytokine availability due to greater irrigation of the bag. We therefore explored the role of growth factor restriction on PCO using human lens cell and tissue culture models. We demonstrate that cytokine dilution, by increasing medium volume, significantly reduced cell coverage in both closed and open capsular bag models. This coincided with reduced cell density and myofibroblast formation. A screen of 27 cytokines identified nine candidates whose expression profile correlated with growth. In particular, VEGF was found to regulate cell survival, growth and myofibroblast formation. VEGF provides a therapeutic target to further manage PCO development and will yield best results when used in conjunction with open bag IOL designs

How hosts control worms

No abstract available

On the stability of high-speed milling with spindle speed variation

Spindle speed variation is a well-known technique to suppress regenerative machine tool vibrations, but it is usually considered to be effective only for low spindle speeds. In this paper, the effect of spindle speed variation is analyzed in the high-speed domain for spindle speeds corresponding to the first flip (period doubling) and to the first Hopf lobes. The optimal amplitudes and frequencies of the speed modulations are computed using the semidiscre- tization method. It is shown that period doubling chatter can effectively be suppressed by spindle speed variation, although, the technique is not effective for the quasiperiodic chatter above the Hopf lobe. The results are verified by cutting tests. Some special cases are also discussed where the practical behavior of the system differs from the predicted one in some ways. For these cases, it is pointed out that the concept of stability is understood on the scale of the principal period of the system—that is, the speed modulation period for variable spindle speed machining and the tooth passing period for constant spindle speed machining

Bilateral Assessment of Functional Tasks for Robot-assisted Therapy Applications

This article presents a novel evaluation system along with methods to evaluate bilateral coordination of arm function on activities of daily living tasks before and after robot-assisted therapy. An affordable bilateral assessment system (BiAS) consisting of two mini-passive measuring units modeled as three degree of freedom robots is described. The process for evaluating functional tasks using the BiAS is presented and we demonstrate its ability to measure wrist kinematic trajectories. Three metrics, phase difference, movement overlap, and task completion time, are used to evaluate the BiAS system on a bilateral symmetric (bi-drink) and a bilateral asymmetric (bi-pour) functional task. Wrist position and velocity trajectories are evaluated using these metrics to provide insight into temporal and spatial bilateral deficits after stroke. The BiAS system quantified movements of the wrists during functional tasks and detected differences in impaired and unimpaired arm movements. Case studies showed that stroke patients compared to healthy subjects move slower and are less likely to use their arm simultaneously even when the functional task requires simultaneous movement. After robot-assisted therapy, interlimb coordination spatial deficits moved toward normal coordination on functional tasks

Maxwell-Chern-Simons Vortices and Holographic Superconductors

We investigate probe limit vortex solutions of a charged scalar field in Einstein-Maxwell theory in 3+1 dimensions, for an asymptotically AdS Schwarzschild black hole metric with the addition of an axionic coupling to the Maxwell field. We show that the inclusion of such a term, together with a suitable potential for the axion field, can induce an effective Chern-Simons term on the 2+1 dimensional boundary. We obtain numerical solutions of the equations of motion and find Maxwell-Chern-Simons like magnetic vortex configurations, where the magnetic field profile varies with the size of the effective Chern-Simons coupling. The axion field has a non-trivial profile inside the AdS bulk but does not condense at spatial infinity.Comment: 17 pages, 5 figures, version accepted for publication in JHE

Review of systematic reviews of non-pharmacological interventions to improve quality of life in cancer survivors.

Over two million people in the UK are living with and beyond cancer. A third report diminished quality of life. A review of published systematic reviews to identify effective non-pharmacological interventions to improve the quality of life of cancer survivors. Databases searched until May 2017 included PubMed, Cochrane Central, EMBASE, MEDLINE, Web of Science, the Cumulative Index to Nursing and Allied Health Literature, and PsycINFO. Published systematic reviews of randomised trials of non-pharmacological interventions for people living with and beyond cancer were included; included reviews targeted patients aged over 18. All participants had already received a cancer diagnosis. Interventions located in any healthcare setting, home or online were included. Reviews of alternative therapies or those non-English reports were excluded. Two researchers independently assessed titles, abstracts and the full text of papers, and independently extracted the data. The primary outcome of interest was any measure of global (overall) quality of life. Quality assessment assessing methdological quality of systematic reviews (AMSTAR) and narrative synthesis, evaluating effectiveness of non-pharmacological interventions and their components. Of 14 430 unique titles, 21 were included in the review of reviews. There was little overlap in the primary papers across these reviews. Thirteen reviews covered mixed tumour groups, seven focused on breast cancer and one focused on prostate cancer. Face-to-face interventions were often combined with online, telephone and paper-based reading materials. Interventions included physical, psychological or behavioural, multidimensional rehabilitation and online approaches. Yoga specifically, physical exercise more generally, cognitive behavioural therapy (CBT) and mindfulness-based stress reduction (MBSR) programmes showed benefit in terms of quality of life. Exercise-based interventions were effective in the short (less than 3-8 months) and long term. CBT and MBSR also showed benefits, especially in the short term. The evidence for multidisciplinary, online and educational interventions was equivocal. [Abstract copyright: © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A Reporter Screen in a Human Haploid Cell Line Identifies CYLD as a Constitutive Inhibitor of NF-κB

The development of forward genetic screens in human haploid cells has the potential to transform our understanding of the genetic basis of cellular processes unique to man. So far, this approach has been limited mostly to the identification of genes that mediate cell death in response to a lethal agent, likely due to the ease with which this phenotype can be observed. Here, we perform the first reporter screen in the near-haploid KBM7 cell line to identify constitutive inhibitors of NF-κB. CYLD was the only currently known negative regulator of NF-κB to be identified, thus uniquely distinguishing this gene. Also identified were three genes with no previous known connection to NF-κB. Our results demonstrate that reporter screens in haploid human cells can be applied to investigate the many complex signaling pathways that converge upon transcription factors

Causal hierarchy within the thalamo-cortical network in spike and wave discharges

Background: Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1. Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy. © 2009 Vaudano et al

Anonymisation of geographical distance matrices via Lipschitz embedding

BACKGROUND: Anonymisation of spatially referenced data has received increasing attention in recent years. Whereas the research focus has been on the anonymisation of point locations, the disclosure risk arising from the publishing of inter-point distances and corresponding anonymisation methods have not been studied systematically. METHODS: We propose a new anonymisation method for the release of geographical distances between records of a microdata file-for example patients in a medical database. We discuss a data release scheme in which microdata without coordinates and an additional distance matrix between the corresponding rows of the microdata set are released. In contrast to most other approaches this method preserves small distances better than larger distances. The distances are modified by a variant of Lipschitz embedding. RESULTS: The effects of the embedding parameters on the risk of data disclosure are evaluated by linkage experiments using simulated data. The results indicate small disclosure risks for appropriate embedding parameters. CONCLUSION: The proposed method is useful if published distance information might be misused for the re-identification of records. The method can be used for publishing scientific-use-files and as an additional tool for record-linkage studies

Transboundary health impacts of transported global air pollution and international trade

Millions of people die every year from diseases caused by exposure to outdoor air pollution1, 2, 3, 4, 5. Some studies have estimated premature mortality related to local sources of air pollution6, 7, but local air quality can also be affected by atmospheric transport of pollution from distant sources8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18. International trade is contributing to the globalization of emission and pollution as a result of the production of goods (and their associated emissions) in one region for consumption in another region14, 19, 20, 21, 22. The effects of international trade on air pollutant emissions23, air quality14 and health24 have been investigated regionally, but a combined, global assessment of the health impacts related to international trade and the transport of atmospheric air pollution is lacking. Here we combine four global models to estimate premature mortality caused by fine particulate matter (PM2.5) pollution as a result of atmospheric transport and the production and consumption of goods and services in different world regions. We find that, of the 3.45 million premature deaths related to PM2.5 pollution in 2007 worldwide, about 12 per cent (411,100 deaths) were related to air pollutants emitted in a region of the world other than that in which the death occurred, and about 22 per cent (762,400 deaths) were associated with goods and services produced in one region for consumption in another. For example, PM2.5 pollution produced in China in 2007 is linked to more than 64,800 premature deaths in regions other than China, including more than 3,100 premature deaths in western Europe and the USA; on the other hand, consumption in western Europe and the USA is linked to more than 108,600 premature deaths in China. Our results reveal that the transboundary health impacts of PM2.5 pollution associated with international trade are greater than those associated with long-distance atmospheric pollutant transport