354 research outputs found
Environmental and productivity management: the business sustainability syndrome
Original article can be found at: http://www.inderscience.com/ Copyright Inderscience Enterprises Limited. DOI: 10.1504/IJETM.2009.021578Every organisation must ensure that its responsibilities are encompassed within its legal, social and economic domains. Environmental and productivity issues thus need to be entwined to form the foundation of such an effective corporate strategy. The inter-relationships of sustainability, growth and the improvement in quality of life are discussed through a stakeholder approach where "greenâ yardsticks are explored and related to productivity. A framework for analysis is constructed, illustrating the flow from inputs, through processes, to outputs and, ultimately, to outcomes, highlighting impacts on society. Such a perspective can be perceived as the contemporary sustainability vision through sensible resource utilisation.Peer reviewe
Longitudinal assessment of reflexive and volitional saccades in Niemann-Pick Type C disease during treatment with miglustat
Peer reviewedPublisher PD
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Role of flavonoids and nitrates in cardiovascular health
CVD remain the leading cause of death globally. Effective dietary strategies for their reduction are of high priority. Increasing evidence suggests that phytochemicals, particularly dietary flavonoids and nitrates, are key modulators of CVD risk reduction through impact on multiple risk factors. The aim of this review is to explore the evidence for the impact of flavonoid- and nitrate-rich foods and supplements on CVD risk, with specific reference to their importance as mediators of vascular health and platelet function. There is accumulating evidence to support benefits of dietary flavonoids on cardiovascular health. Dose-dependent recovery of endothelial function and lowering of blood pressure have been reported for the flavanol (-)-epicatechin, found in cocoa, apples and tea, through production and availability of endothelial nitric oxide (NO). Furthermore, flavonoids, including quercetin and its metabolites, reduce in vitro and ex vivo platelet function via inhibition of phosphorylation-dependent cellular signalling pathways, although further in vivo studies are required to substantiate these mechanistic effects. Hypotensive effects of dietary nitrates have been consistently reported in healthy subjects in acute and chronic settings, although there is less evidence for these effects in patient groups. Proposed mechanisms of actions include endothelial-independent NO availability, which is dependent on the entro-salivary circulation and microbial conversion of dietary nitrate to nitrite in the mouth. In conclusion, flavonoid- and nitrate-rich foods show promising effects on vascular function, yet further randomly controlled studies are required to confirm these findings and to determine effective doses
Photoluminescence upconversion at GaAs/InGaP2 interfaces driven by a sequential two-photon absorption mechanism
This paper reports on the results of an investigation into the nature of photoluminescence upconversion at
GaAs/InGaP2 interfaces. Using a dual-beam excitation experiment, we demonstrate that the upconversion in our
sample proceeds via a sequential two-photon optical absorption mechanism. Measurements of photoluminescence
and upconversion photoluminescence revealed evidence of the spatial localization of carriers in the InGaP2
material, arising from partial ordering of the InGaP2. We also observed the excitation of a two-dimensional electron
gas at the GaAs/InGaP2 heterojunction that manifests as a high-energy shoulder in the GaAs photoluminescence
spectrum. Furthermore, the results of upconversion photoluminescence excitation spectroscopy demonstrate that
the photon energy onset of upconversion luminescence coincides with the energy of the two-dimensional electron
gas at the GaAs/InGaP2 interface, suggesting that charge accumulation at the interface can play a crucial role in
the upconversion process
An evaluation of the progress made towards the implementation of treatment summaries for cancer patients across Wessex
This report details an evaluation of the implementation of treatment summaries for cancer patients across the Wessex Deanery, encompassing Hampshire, Dorset and the Isle of Wight. The service evaluation commenced at the end of September 2015 and this report presents the progress made towards the implementation of cancer treatment summaries (CT) across the Wessex Deanery and service usersâ experiences of receiving the TSs from two NHS Trusts in the catchment area. The survey results present the progress that has been made in the first six months of implementation and include descriptive data relating to the progress and process of implementation. The qualitative findings from an analysis of service user experience are presented and the findings from the evaluation are discussed in the context of national policy and the wider literature
Interstitial pneumonia with autoimmune features: Why rheumatologistâpulmonologist collaboration is essential
In 2015 the European Respiratory Society (ERS) and the American Thoracic Society (ATS) âTask Force on Undifferentiated Forms of Connective Tissue Disease-associ-ated Interstitial Lung Diseaseâ proposed classification criteria for a new research category defined as âInterstitial Pneumonia with Autoimmune Featuresâ (IPAF), to uniformly de-fine patients with interstitial lung disease (ILD) and features of autoimmunity, without a definite connective tissue disease. These classification criteria were based on a variable combination of features obtained from three domains: a clinical domain consisting of extra-thoracic features, a serologic domain with specific autoantibodies, and a morphologic domain with imaging patterns, histopathological findings, or multicompartment in-volvement. Features suggesting a systemic vasculitis were excluded. Since publication of ERS/ATS IPAF research criteria, various retrospective studies have been published focusing on prevalence; clinical, morphological, and serological features; and prognosis of these patients showing a broad heterogeneity in the results. Recently, two prospective, cohort studies were performed, confirming the existence of some peculiarities for this clinical entity and the possible progression of IPAF to a defined connective tissue disease (CTD) in about 15% of cases. Moreover, a non-specific interstitial pneumonia pattern, an anti-nuclear antibody positivity, and a Raynaud phenomenon were the most common findings. In comparison with idiopathic pulmonary fibrosis (IPF), IPAF patients showed a better performance in pulmonary function tests and less necessity of oxygen delivery. However, at this stage of our knowledge, we believe that further prospective studies, possibly derived from multicenter cohorts and through randomized control trials, to further validate the proposed classification criteria are needed
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Ibrutinib inhibits platelet integrin αIIbÎČ3 outside-in signaling and thrombus stability but not adhesion to collagen
OBJECTIVE:
Ibrutinib is an irreversible Bruton tyrosine kinase inhibitor approved for treatment of Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, and mantle cell lymphoma that increases the risk of bleeding among patients. Platelets from ibrutinib-treated patients exhibit deficiencies in collagen-evoked signaling in suspension; however, the significance of this observation and how it relates to bleeding risk is unclear, as platelets encounter immobile collagen in vivo. We sought to clarify the effects of ibrutinib on platelet function to better understand the mechanism underlying bleeding risk.
APPROACH AND RESULTS:
By comparing signaling in suspension and during adhesion to immobilized ligands, we found that the collagen signaling deficiency caused by ibrutinib is milder during adhesion to immobilized collagen. We also found that platelets in whole blood treated with ibrutinib adhered to collagen under arterial shear but formed unstable thrombi, suggesting that the collagen signaling deficiency caused by ibrutinib may not be the predominant cause of bleeding in vivo. However, clot retraction and signaling evoked by platelet adhesion to immobilized fibrinogen were also inhibited by ibrutinib, indicating that integrin αIIbÎČ3 outside-in signaling is also effected in addition to GPVI signaling. When ibrutinib was combined with the P2Y12 inhibitor, cangrelor, thrombus formation under arterial shear was inhibited additively.
CONCLUSIONS:
These findings suggest that (1) ibrutinib causes GPVI and integrin αIIbÎČ3 platelet signaling deficiencies that result in formation of unstable thrombi and may contribute toward bleeding observed in vivo and (2) combining ibrutinib with P2Y12 antagonists, which also inhibit thrombus stability, may have a detrimental effect on hemostasis
Photoluminescence upconversion at interfaces driven by a sequential two-photon absorption mechanism
This paper reports on the results of an investigation into the nature of photoluminescence upconversion at
GaAs/InGaP2 interfaces. Using a dual-beam excitation experiment, we demonstrate that the upconversion in our
sample proceeds via a sequential two-photon optical absorption mechanism. Measurements of photoluminescence
and upconversion photoluminescence revealed evidence of the spatial localization of carriers in the InGaP2
material, arising from partial ordering of the InGaP2. We also observed the excitation of a two-dimensional electron
gas at the GaAs/InGaP2 heterojunction that manifests as a high-energy shoulder in the GaAs photoluminescence
spectrum. Furthermore, the results of upconversion photoluminescence excitation spectroscopy demonstrate that
the photon energy onset of upconversion luminescence coincides with the energy of the two-dimensional electron
gas at the GaAs/InGaP2 interface, suggesting that charge accumulation at the interface can play a crucial role in
the upconversion process
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A humanized monoclonal antibody that inhibits platelet-surface ERp72 reveals a role for ERp72 in thrombosis
Background: Within the endoplasmic reticulum, thiol isomerase enzymes modulate the formation and rearrangement of disulphide bonds in newly folded proteins entering the secretory pathway to ensure correct protein folding. In addition to their intracellular importance, thiol isomerases have been recently identified to be present on the surface of a number of cell types where they are important for cell function. Several thiol isomerases are known to be present on the resting platelet surface including PDI, ERp5 and ERp57 and levels are increased following platelet activation. Inhibition of the catalytic activity of these enzymes results in diminished platelet function and thrombosis.
Aim: We previously determined that ERp72 is present at the resting platelet surface and levels increase upon platelet activation, however its functional role on the cell surface was unclear. We aimed to investigate the role of ERp72 in platelet function and its role in thrombosis.
Methods: Using HuCAL technology, fully humanised Fc-null anti-ERp72 antibodies were generated. Eleven antibodies were screened for their ability to inhibit ERp72 activity and the most potent inhibitory antibody (anti-ERp72) selected for further testing in platelet functional assays.
Results and conclusions: Anti-ERp72 inhibited platelet aggregation, granule secretion, calcium mobilisation and integrin activation revealing an important role for extracellular ERp72 in the regulation of platelet activation. Consistent with this, infusion of anti-ERp72 into mice protected against thrombosis
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