Supernatants derived from chemotherapy-treated cancer cell lines can modify angiogenesis

BACKGROUND: There is evidence that tumours produce substances such as cytokines and microvesicular bodies bearing bioactive molecules, which support the carcinogenic process. Furthermore, chemotherapy has also been shown to modify these exudates and in doing so, neutralise their tumourigenic influence. METHODS: In the current study, we have investigated the effect of chemotherapy agents on modifying the cytokine profile and microvesicular cargo of supernatants derived from cancer cell lines. In addition, we have explored the effect of these tumour-derived supernatants on angiogenesis, and how chemotherapy can alter the supernatants rendering them less pro-angiogenic. RESULTS: Herein, we show that supernatants contain a rich cocktail of cytokines, a number of which are potent modulators of angiogenesis. They also contain microvesicular bodies containing RNA transcripts that code for proteins involved in transcription, immune modulation and angiogenesis. These supernatants altered intracellular signalling molecules in endothelial cells and significantly enhanced their tubulogenic character; however, this was severely compromised when supernatants from tumours treated with chemotherapy was used instead. CONCLUSION: This study suggests tumour exudates and bioactive material from tumours can influence cellular functions, and that treatment with some chemotherapy can serve to negate these pro-tumourigenic processes

Demonstration of multi-channel 80 Gbit/s integrated transmitter and receiver for wavelength-division multiplexing passive optical network and fronthauling applications

The performance evaluation of a multi-channel transmitter that employs an arrayed reflective electroabsorption modulator-based photonic integrated circuit and a low-power driver array in conjunction with a multi-channel receiver incorporating a pin photodiode array and integrated arrayed waveguide grating is reported. Due to their small footprint, low power consumption and potential low cost, these devices are attractive solutions for future mobile fronthaul and next generation optical access networks. A BER performance of <10(-9) at 10.3 Gbit/s per channel is achieved over 25 km of standard single mode fibre. The transmitter/receiver combination can achieve an aggregate bit rate of 82.4 Gbit/s when eight channels are active

Novel translational model of resolving inflammation triggered by UV-killed E. coli

Whilst numerous studies investigating the aetiology of inflammatory diseases have been performed in rodents, the applicability of these data to human pathophysiology is frequently debated. Regardless of the strengths and weaknesses of rodent models in biomedical research, there is a need to develop models of experimental inflammation in humans. Here, we describe a self-resolving acute inflammatory response triggered by the intradermal injection of UV-killed Escherichia coli into the forearm of healthy volunteers. Cells and exudates were harvested from onset to resolution by applying negative pressure over the inflamed site. Onset was characterized by high blood flow, neutrophilia and peak levels of pro-inflammatory cytokines, whilst resolution showed a decline in blood blow, reduction in neutrophils, increase in monocytes/macrophages and waning of classic pro-inflammatory cytokine levels. An anti-inflammatory effect, defined as suppression of onset phase events, was demonstrated by administering naproxen, a conventional non-steroidal anti-inflammatory drug. In summary, this model of resolving acute inflammation is minimally invasive, highly tractable and allows simultaneous investigation of the vascular response, cellular trafficking and chemical mediator profile of onset and resolution phases of acute inflammation in humans. It can serve as a translational platform to provide mechanistic insights and to test the clinical efficacy of novel anti-inflammatory and pro-resolving drugs, and also as a tool in patients to explore inherent defects in resolution pathways

Municipal water quantities and health in Nunavut households: an exploratory case study in Coral Harbour, Nunavut, Canada

Background: Access to adequate quantities of water has a protective effect on human health and well-being. Despite this, public health research and interventions are frequently focused solely on water quality, and international standards for domestic water supply minimums are often overlooked or unspecified. This trend is evident in Inuit and other Arctic communities even though numerous transmissible diseases and bacterium infections associated with inadequate domestic water quantities are prevalent. Objectives: Our objective was to explore the pathways by which the trucked water distribution systems being used in remote northern communities are impacting health at the household level, with consideration given to the underlying social and environmental determinants shaping health in the region. Methods: Using a qualitative case study design, we conducted 37 interviews (28 residents, 9 key informants) and a review of government water documents to investigate water usage practices and perspectives. These data were thematically analysed to understand potential health risks in Arctic communities and households. Results: Each resident receives an average of 110 litres of municipal water per day. Fifteen of 28 households reported experiencing water shortages at least once per month. Of those 15, most were larger households (5 people or more) with standard sized water storage tanks. Water shortages and service interruptions limit the ability of some households to adhere to public health advice. The households most resilient, or able to cope with domestic water supply shortages, were those capable of retrieving their own drinking water directly from lake and river sources. Residents with extended family and neighbours, whom they can rely on during shortages, were also less vulnerable to municipal water delays. Conclusions: The relatively low in-home water quantities observed in Coral Harbour, Nunavut, appear adequate for some families. Those living in overcrowded households, however, are accessing water in quantities more typically seen in water insecure developing countries. We recommend several practical interventions and revisions to municipal water supply systems

Modelling rotational failure in confined geometries using DLO

Discontinuity layout optimisation (DLO) is a generally applicable numerical limit analysis procedure that can be used to identify critical plastic collapse mechanisms in engineering problems. Considering the modelling of in-plane failure, the authors have previously presented a formulation capable of identifying rotational failure mechanisms in non-dilating media. However, the formulation presented did not explicitly address cases involving confined geometries, where curved slip lines could potentially intersect boundaries. In this paper, methods are outlined which permit efficient modelling of such cases. Details of the kinematic and equilibrium formulations are provided, which are then verified through application to various geotechnical and structural mechanics problems. It is shown that results of high accuracy can be obtained, both in terms of the predicted collapse load and the corresponding failure mechanism

Nonlinear axisymmetric elastic analysis of deep imperfect spherical shells

The particular problem that is addressed in this thesis is the nonlinear elastic analysis of incomplete thin deep spherical shells, where the displacements on the boundary surface are fully restrained and the shell is loaded by a uniform pressure load. The shell may contain initial axisymmetric geometric or stress imperfections, and the initial response of the shell, the fundamental path, is axisymmetric. Solution techniques are developed and presented for the nonlinear fundamental path, and the nonlinear eigenvalue problem that yields the location of the points of the axisymmetric or periodic secondary paths that bifurcate from the axisymmetric fundamental path and the initial mode shapes of the secondary paths at the point of bifurcation of the secondary paths from the nonlinear axisymmetric fundamental path. Using the nonlinear elastic deep shell theory developed in this thesis, the behaviour of perfect and imperfect incomplete spherical shells with fully restrained boundary surface displacements under uniform pressure loading is examined. This thesis also attempts to derive and present the equations and solution methods used in the nonlinear elastic analysis of thin spherical caps in as general a way as possible, in order that the solution methods developed in the thesis may be applied to shell structures composed of one or more incomplete thin elastic shells of arbitrary shape under arbitrary loading. By extending the derivation of the strain-displacement expressions for shells to include the terms that are quartic in displacements, the limitations present in linear thin shell theory may be lifted, and partial differential equations governing the nonlinear elastic behaviour of thin shells of arbitrary shape may be developed. The methods used to develop the total potential energy functional for pressure loaded spherical shells may be extended and used to express the total potential energy of shell structures composed of one or more incomplete shells of arbitrary shape under arbitrary loading

Assessing the capacity of local ecosystems to meet industrial demand for ecosystem services

Despite the importance of ecosystems, engineering activities continue to ignore or greatly undervalue their role. Consequently, engineered systems often overshoot nature's capacity to support them, causing ecological degradation. Such systems tend to be inherently unsustainable, and they often fail to benefit from nature's ability to provide essential goods and services. This work explores the idea of including ecosystems in chemical processes, and assesses whether such a techno-ecological synergistic system can operate within ecological constraints. The demand for ecosystem services is quantified by emissions and resources used, while the supply is provided by ecosystems on the manufacturing site. Application to a biodiesel manufacturing site demonstrates that ecosystems can be economically and environmentally superior to conventional technologies for making progress toward zero emissions and net positive impact manufacturing. These results highlight the need for shifting the paradigm of engineering from that of dominating nature to embracing nature and respecting its limits

Analysis of bolted flanged panel joint for GRP sectional tanks

Peer reviewedPublisher PD

Challenges and Opportunities: What Can We Learn from Patients Living with Chronic Musculoskeletal Conditions, Health Professionals and Carers about the Concept of Health Literacy Using Qualitative Methods of Inquiry?

The field of health literacy continues to evolve and concern public health researchers and yet remains a largely overlooked concept elsewhere in the healthcare system. We conducted focus group discussions in England UK, about the concept of health literacy with older patients with chronic musculoskeletal conditions (mean age = 73.4 years), carers and health professionals. Our research posed methodological, intellectual and practical challenges. Gaps in conceptualisation and expectations were revealed, reiterating deficiencies in predominant models for understanding health literacy and methodological shortcomings of using focus groups in qualitative research for this topic. Building on this unique insight into what the concept of health literacy meant to participants, we present analysis of our findings on factors perceived to foster and inhibit health literacy and on the issue of responsibility in health literacy. Patients saw health literacy as a result of an inconsistent interactive process and the implications as wide ranging; healthcare professionals had more heterogeneous views. All focus group discussants agreed that health literacy most benefited from good inter-personal communication and partnership. By proposing a needs-based approach to health literacy we offer an alternative way of conceptualising health literacy to help improve the health of older people with chronic conditions