Turning Brownfields into Jobfields

A handbook for practitioners and citizens on making brownfields development work

Integration of informal music technologies in secondary school music lessons

date-added: 2011-08-12 11:03:06 +0100 date-modified: 2011-08-12 11:03:38 +0100date-added: 2011-08-12 11:03:06 +0100 date-modified: 2011-08-12 11:03:38 +0100This project was supported by EPSRC grant EP/I001832/1, ‘Musicology for the masses’

Fighting the Infodemic on Two Fronts: Reducing False Beliefs Without Increasing Polarization

Actors aiming to remedy the effects of health misinformation often issue corrections focused on individual outcomes (i.e., promoting individual health behaviors) rather than societal outcomes (i.e., reducing issue polarization). Yet, for highly politicized health crises like the COVID-19 pandemic, such interventions run the risk of exacerbating societal cleavages, driving those holding opposing views further apart from one another. Interventions yielding individual benefits but causing societal harm are certainly not ideal. But is the design of such dual-focus corrections even possible? We believe this to be the case. Here, we delineate an agenda for future research that should help social scientists in identifying the characteristics of corrections that might reduce false beliefs without increasing polarization

Stress granules in colorectal cancer: Current knowledge and potential therapeutic applications

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.Stress granules (SGs) represent important non-membrane cytoplasmic compartments, involved in cellular adaptation to various stressful conditions (e.g., hypoxia, nutrient deprivation, oxidative stress). These granules contain several scaffold proteins and RNA-binding proteins, which bind to mRNAs and keep them translationally silent while protecting them from harmful conditions. Although the role of SGs in cancer development is still poorly known and vary between cancer types, increasing evidence indicate that the expression and/or the activity of several key SGs components are deregulated in colorectal tumors but also in pre-neoplastic conditions (e.g., inflammatory bowel disease), thus suggesting a potential role in the onset of colorectal cancer (CRC). It is therefore believed that SGs formation importantly contributes to various steps of colorectal tumorigenesis but also in chemoresistance. As CRC is the third most frequent cancer and one of the leading causes of cancer mortality worldwide, development of new therapeutic targets is needed to offset the development of chemoresistance and formation of metastasis. Abolishing SGs assembly may therefore represent an appealing therapeutic strategy to re-sensitize colon cancer cells to anti-cancer chemotherapies. In this review, we summarize the current knowledge on SGs in colorectal cancer and the potential therapeutic strategies that could be employed to target them

Experiences with AR plots: A travel time augmented reality game

Digital games have the potential for changing attitudes towards social issues such as climate change and sustainability. These games don’t have to be based on fixed computing and with the rise of smart phone, they can make use of a range of sensor and augmented reality technologies. This paper presents the experience of developing AR Plots, a prototype locative game with an augmented reality interface. It is a game designed to fit in with the fractured nature of travel time on public transport. This paper discusses technical challenges, usability issues and game design approaches used to work within these constraints

CRC-derived exosomes containing the RNA binding protein HuR promote lung cell proliferation by stabilizing c-Myc mRNA

HuR overexpression is related to poor survival in patients with colon cancer. HuR overexpression leads to stabilization of tumor-promoting mRNAs by binding to 3′UTR-resident AREs. Exosomes, nanosized lipid bilayer vesicles, mediate many steps in cancer progression. The potential role of exosomal HuR in colon cancer lung metastasis is unclear. HuR expression was assessed immunohistochemically in tumor tissue samples from 20 patients with metastatic or nonmetastatic colon cancer and colon cancer lung metastasis and benign lung disease samples from ten patients. Exosomes were isolated from HCT116 WT and HuR KO colon cancer cells, and uptake of PKH67- and PKH26-labeled exosomes by BEAS-2B cells was evaluated using fluorescence and confocal microscopy. C-Myc and p21protein and mRNA levels were measured by western blotting and RT-qPCR, respectively. In clinical patients, HuR overexpression was significantly enhanced in colon tissues of patients with lung metastasis. HuR expression was higher in lung tissue with metastasis of colonic origin than with benign lung disease. The effect of HuR-containing CRC exosomes compared to HuR-deficient exosomes on wound closure was observed as enhanced proliferation. BEAS-2B cell migration and invasion were enhanced after HuR-containing exosomes treatment. BEAS-2B cells showed similar uptake of PKH67 (HCT116 WT)- and PKH26 (HCT116 HuR KO)-labeled exosomes. Exosomal HuR stabilized c-Myc mRNA and downregulated p21 expression, leading to G1/S transition, in human bronchial epithelial cells. HuR overexpression is associated with lung metastasis in colon cancer patients. Exosomal HuR derived from colon cancer cells alter the biological effect on normal lung epithelial cells

Non-union following bilateral simultaneos Ganz trochanteric osteotomy

Between January 2003 and December 2004, 13 patients underwent bilateral resurfacing arthroplasty via a Ganz trochanteric osteotomy. This bilateral group was mobilised fully weight-bearing with crutches. During the same period 139 Ganz trochanteric osteotomies were performed for unilateral hip resurfacing. These patients were mobilised with crutches, weight-bearing up to 10 kg on the operated leg. Nine osteotomies (32%) in the bilateral group subsequently developed a symptomatic non-union requiring revision of fixation. This compares with 10 patients (7%) in the unilateral group. Applying the Fisher's exact test, the difference reached significance (P=0.0004). In two patients a second revision was required to achieve union. In one patient, revision of trochanteric fixation precipitated a deep infection. Protected weight-bearing following a Ganz trochanteric osteotomy is important to the success of the procedure. Simultaneous bilateral hip arthroplasty through a Ganz approach should be avoided. If it is undertaken, we recommend that patients should be non weight-bearing for 6 weeks following surgery. Non-union following a Ganz trochanteric osteotomy for arthroplasty carries a significant morbidity

Point of care blood tests during home visits by out-of-hours primary care clinicians; a mixed methods evaluation of a service improvement

Objectives We aimed to evaluate test usage and patient and clinician experience following the introduction of point-of-care (POC) blood tests into a primary care out-of-hours service. Design A mixed methods service evaluation comprising quantitative records of the clinical contexts of tests taken and qualitative interviews with clinicians. Research permissions and governance were obtained for patient interviews. Setting Out-of-hours primary care. Participants All patients requiring home visits from the service during the implementation period. Interventions The i-STAT POC blood test platform was introduced to two bases providing home visits for a period of 8 months. Venous blood samples were used and two cartridges were available. The CHEM8 cartridge measures sodium, potassium, chloride, total carbon dioxide (TCO2), anion gap, ionised calcium, glucose, urea, creatinine, haematocrit and haemoglobin. The CG4 cartridge measures lactate, pH, PaO2 and PCO2, TCO2, bicarbonate, base excess and oxygen saturation. Primary and secondary outcome measures The proportion of home visits where tests were taken, the clinical contexts of those tests, the extent to which clinicians felt the tests had influenced their decisions, time taken to perform the test and problems encountered. Clinician and patient experiences of using POC tests. Results i-STAT POC tests were infrequently used, with successful tests taken at just 47 contacts over 8 months of implementation. The patients interviewed felt that testing had been beneficial for their care. Clinician interviews suggested barriers to POC tests, including practical challenges, concerns about time, doubt over whether they would improve clinical decision making and concern about increased medicolegal risk. Suggestions for improving adoption included sharing learning, adopting a whole team approach and developing protocols for usage. Conclusions POC tests were not successfully adopted by an out-of-hours home visiting service in Oxfordshire. While some clinicians felt they could not add value, in other cases they resulted in improved patient experience. Adoption could be promoted by improving technical, team and education factors

Impact of HuR inhibition by the small molecule MS-444 on colorectal cancer cell tumorigenesis.

Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related mortality. Observed during CRC tumorigenesis is loss of post-transcriptional regulation of tumor-promoting genes such as COX-2, TNFα and VEGF. Overexpression of the RNA-binding protein HuR (ELAVL1) occurs during colon tumorigenesis and is abnormally present within the cytoplasm, where it post-transcriptionally regulates genes through its interaction with 3\u27UTR AU-rich elements (AREs). Here, we examine the therapeutic potential of targeting HuR using MS-444, a small molecule HuR inhibitor. Treatment of CRC cells with MS-444 resulted in growth inhibition and increased apoptotic gene expression, while similar treatment doses in non-transformed intestinal cells had no appreciable effects. Mechanistically, MS-444 disrupted HuR cytoplasmic trafficking and released ARE-mRNAs for localization to P-bodies, but did not affect total HuR expression levels. This resulted in MS-444-mediated inhibition of COX-2 and other ARE-mRNA expression levels. Importantly, MS-444 was well tolerated and inhibited xenograft CRC tumor growth through enhanced apoptosis and decreased angiogenesis upon intraperitoneal administration. In vivo treatment of MS-444 inhibited HuR cytoplasmic localization and decreased COX-2 expression in tumors. These findings provide evidence that therapeutic strategies to target HuR in CRC warrant further investigation in an effort to move this approach to the clinic