Treating Water Contamination using Ultraviolet Radiation to Control Cryptosporidium and E.Coli

Concerns about the quality of drinking water in Ireland have come into sharp focus with the recent Cryptosporidium outbreak in Galway City. This article looks at how ultraviolet radiation can offer a potential solution in the control of Cryptosporidium contamination

Invisible design: exploring insights and ideas through ambiguous film scenarios

Invisible Design is a technique for generating insights and ideas with workshop participants in the early stages of concept development. It involves the creation of ambiguous films in which characters discuss a technology that is not directly shown. The technique builds on previous work in HCI on scenarios, persona, theatre, film and ambiguity. The Invisible Design approach is illustrated with three examples from unrelated projects; Biometric Daemon, Panini and Smart Money. The paper presents a qualitative analysis of data from a series of workshops where these Invisible Designs were discussed. The analysis outlines responses to the films in terms of; existing problems, concerns with imagined technologies and design speculation. It is argued that Invisible Design can help to create a space for critical and creative dialogue during participatory concept development

Understanding exercise referrals in primary care: a qualitative study of General Practitioners and physiotherapists

Background: Physical inactivity is estimated to cost the UK National Health Service over £7.4 billion per year. Healthcare practitioners have a key role in supporting increases in physical activity (PA) levels, including referring to exercise referral schemes. To date, there has been little research into practitioner perspectives on referrals to exercise schemes. Objectives: To explore the views and experiences of General Practitioners (GPs) and physiotherapists in relation to factors which influence referral and adherence to exercise referral schemes. Design setting & participants: Qualitative study of primary care-based practitioners in Glasgow, UK. Methods: Semi-structured interviews were conducted with 14 practitioners (seven GPs and seven physiotherapists). Interviews were recorded and analysed thematically. Results: Four themes are presented. Firstly, all people, including healthcare practitioners, bring inherent biases which are influenced by their background, experiences and worldviews to a consultation which impact their approach to PA promotion. Secondly, clinical time pressures are a major barrier to effective PA promotion. Thirdly, patient-led, compassionate care which seeks to fully understand a patient is the most vital component of behaviour change, with suggestions that promoting peer support and the use of personal anecdotes to normalise vulnerabilities might be helpful. Lastly, providing ongoing support for change was felt to be beneficial to PA promotion. This is often accessed through exercise referral schemes and improved by better collaboration between exercise providers and referring practitioners. Conclusion: Practitioners believed exercise referrals could be improved with more targeted training in behaviour change facilitation, support for multidisciplinary working, and enhanced communication between the programmes and referrers. Additionally, supporting behaviour change requires time for compassionate care and fully understanding patients’ motivations and beliefs. Lack of time was felt to be the greatest current barrier to effective PA promotion

Metabolism of tissue macrophages in homeostasis and pathology.

Cellular metabolism orchestrates the intricate use of tissue fuels for catabolism and anabolism to generate cellular energy and structural components. The emerging field of immunometabolism highlights the importance of cellular metabolism for the maintenance and activities of immune cells. Macrophages are embryo- or adult bone marrow-derived leukocytes that are key for healthy tissue homeostasis but can also contribute to pathologies such as metabolic syndrome, atherosclerosis, fibrosis or cancer. Macrophage metabolism has largely been studied in vitro. However, different organs contain diverse macrophage populations that specialize in distinct and often tissue-specific functions. This context specificity creates diverging metabolic challenges for tissue macrophage populations to fulfill their homeostatic roles in their particular microenvironment and conditions their response in pathological conditions. Here, we outline current knowledge on the metabolic requirements and adaptations of macrophages located in tissues during homeostasis and selected diseases.SKW and the project that gave rise to these results received support in the form of a fellowship from the La Caixa Foundation (ID 100010434). The fellowship code is LCF/BQ/ PR20/11770008. GD is supported by a European Molecular Biology Organization Longterm Fellowship (ALTF 379-2019). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie SkłodowskaCurie grant agreement No. 892965. IHM is supported by a La Caixa INPhINIT fellowship (ID 100010434, fellowship code: LCF/BQ/IN17/11620074). Work in the DS laboratory is funded by the CNIC, by the European Research Council (ERC-2016-Consolidator Grant 725091), by the Agencia Estatal de Investigación (PID2019-108157RB), by the Comunidad de Madrid (B2017/BMD-3733 Immunothercan-CM), by Atresmedia (Constantes y Vitales prize), by the Fondo Solidario Juntos (Banco Santander), and by the Fundació La Marató de TV3 (201723). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the MICINN and the Pro CNIC Foundation.S

The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers.

Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes

Transportation Energy Pathways LDRD.

This report presents a system dynamics based model of the supply-demand interactions between the USlight-duty vehicle (LDV) fleet, its fuels, and the corresponding primary energy sources through the year2050. An important capability of our model is the ability to conduct parametric analyses. Others have reliedupon scenario-based analysis, where one discrete set of values is assigned to the input variables and used togenerate one possible realization of the future. While these scenarios can be illustrative of dominant trendsand tradeoffs under certain circumstances, changes in input values or assumptions can have a significantimpact on results, especially when output metrics are associated with projections far into the future. Thistype of uncertainty can be addressed by using a parametric study to examine a range of values for the inputvariables, offering a richer source of data to an analyst.The parametric analysis featured here focuses on a trade space exploration, with emphasis on factors thatinfluence the adoption rates of electric vehicles (EVs), the reduction of GHG emissions, and the reduction ofpetroleum consumption within the US LDV fleet. The underlying model emphasizes competition between13 different types of powertrains, including conventional internal combustion engine (ICE) vehicles, flex-fuel vehicles (FFVs), conventional hybrids(HEVs), plug-in hybrids (PHEVs), and battery electric vehicles(BEVs).We find that many factors contribute to the adoption rates of EVs. These include the pace of technologicaldevelopment for the electric powertrain, battery performance, as well as the efficiency improvements inconventional vehicles. Policy initiatives can also have a dramatic impact on the degree of EV adoption. Theconsumer effective payback period, in particular, can significantly increase the market penetration rates ifextended towards the vehicle lifetime.Widespread EV adoption can have noticeable impact on petroleum consumption and greenhouse gas(GHG) emission by the LDV fleet. However, EVs alone cannot drive compliance with the most aggressiveGHG emission reduction targets, even as the current electricity source mix shifts away from coal and towardsnatural gas. Since ICEs will comprise the majority of the LDV fleet for up to forty years, conventional vehicleefficiency improvements have the greatest potential for reductions in LDV GHG emissions over this time.These findings seem robust even if global oil prices rise to two to three times current projections. Thus,investment in improving the internal combustion engine might be the cheapest, lowest risk avenue towardsmeeting ambitious GHG emission and petroleum consumption reduction targets out to 2050.3 AcknowledgmentThe authors would like to thank Dr. Andrew Lutz, Dr. Benjamin Wu, Prof. Joan Ogden and Dr. ChristopherYang for their suggestions over the course of this project. This work was funded by the Laboratory DirectedResearch and Development program at Sandia National Laboratories.

Combining hyperspectral imaging and electrochemical sensing for detection of Pseudomonas aeruginosa through pyocyanin production

Despite bacterial biofilms representing a common form of infection, notably on medical devices post implantation, their detection and characterisation with existing methods is not sufficient to inform clinicians about biofilm presence or treatment response in affected patients. This study reports the development and use of a combined hyperspectral imaging (HSI) and electrochemical platform to monitor biofilm formation optically and electrochemically. Firstly, production of pyocyanin, a common pigmented and redox active secondary metabolite produced by P. aeruginosa, is monitored by combined HSI and square-wave voltammetry. Secondly, P. aeruginosa biofilm formation is characterised directly using electrochemical impedance spectroscopy. This suite of optical and electrochemical measurements allows for combined monitoring of secondary metabolite/virulence factor production along with direct monitoring of biofilm formation on the sensor surface. Crucially, the easy to deploy and low-cost nature of the selected sensing technologies means the approach can be developed for enhanced study of biofilms and/or at the point of care

The Role of Lipolysis Stimulated Lipoprotein Receptor in Breast Cancer and Directing Breast Cancer Cell Behavior

The claudin-low molecular subtype of breast cancer is of particular interest for clinically the majority of these tumors are poor prognosis, triple negative, invasive ductal carcinomas. Claudin-low tumors are characterized by cancer stem cell-like features and low expression of cell junction and adhesion proteins. Herein, we sought to define the role of lipolysis stimulated lipoprotein receptor (LSR) in breast cancer and cancer cell behavior as LSR was recently correlated with tumor-initiating features. We show that LSR was expressed in epithelium, endothelium, and stromal cells within the healthy breast tissue, as well as in tumor epithelium. In primary breast tumor bioposies, LSR expression was significantly correlated with invasive ductal carcinomas compared to invasive lobular carcinomas, as well as ERα positive tumors and breast cancer cell lines. LSR levels were significantly reduced in claudin-low breast cancer cell lines and functional studies illustrated that re-introduction of LSR into a claudin-low cell line suppressed the EMT phenotype and reduced individual cell migration. However, our data suggest that LSR may promote collective cell migration. Re-introduction of LSR in claudin-low breast cancer cell lines reestablished tight junction protein expression and correlated with transepithelial electrical resistance, thereby reverting claudin-low lines to other intrinsic molecular subtypes. Moreover, overexpression of LSR altered gene expression of pathways involved in transformation and tumorigenesis as well as enhanced proliferation and survival in anchorage independent conditions, highlighting that reestablishment of LSR signaling promotes aggressive/tumor initiating cell behaviors. Collectively, these data highlight a direct role for LSR in driving aggressive breast cancer behavior

A novel assay of antimycobacterial activity and phagocytosis by human neutrophils

SummaryDespite abundant evidence that neutrophils arrive early at sites of mycobacterial disease and phagocytose organisms, techniques to assay phagocytosis or killing of mycobacteria by these cells are lacking. Existing assays for measuring the antimycobacterial activity of human leukocytes require cell lysis which introduces new bioactive substances and may be incomplete. They are also time-consuming and carry multiple risks of inaccuracy due to serial dilution and organism clumping. Flow cytometric techniques for measuring phagocytosis of mycobacteria by human cells have failed to adequately address the effects of organism clumping, quenching agents and culture conditions on readouts.Here we present a novel in-tube bioluminescence-based assay of antimycobacterial activity by human neutrophils. The assay yields intuitive results, with improving restriction of mycobacterial bioluminescence as the ratio of cells to organisms increases. We show that lysis of human cells is not required to measure luminescence accurately.We also present a phagocytosis assay in which we have minimised the impact of mycobacterial clumping, investigated the effect of various opsonisation techniques and established the correct usage of trypan blue to identify surface-bound organisms without counting dead cells. The same multiplicity of infection and serum conditions are optimal to demonstrate both internalisation and restriction of mycobacterial growth