FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity

From Springer Nature via Jisc Publications RouterHistory: received 2020-06-29, accepted 2021-03-15, registration 2021-04-23, pub-electronic 2021-05-28, online 2021-05-28, collection 2021-12Publication status: PublishedFunder: Royal College of Surgeons of England (RCS); doi: https://doi.org/10.13039/501100000297Abstract: Cancer stem-like cells (CSC) contribute to therapy resistance and recurrence. Focal adhesion kinase (FAK) has a role in CSC regulation. We determined the effect of FAK inhibition on breast CSC activity alone and in combination with adjuvant therapies. FAK inhibition reduced CSC activity and self-renewal across all molecular subtypes in primary human breast cancer samples. Combined FAK and paclitaxel reduced self-renewal in triple negative cell lines. An invasive breast cancer cohort confirmed high FAK expression correlated with increased risk of recurrence and reduced survival. Co-expression of FAK and CSC markers was associated with the poorest prognosis, identifying a high-risk patient population. Combined FAK and paclitaxel treatment reduced tumour size, Ki67, ex-vivo mammospheres and ALDH+ expression in two triple negative patient derived Xenograft (PDX) models. Combined treatment reduced tumour initiation in a limiting dilution re-implantation PDX model. Combined FAK inhibition with adjuvant therapy has the potential to improve breast cancer survival

Potential Contributions to Geoscience from GNSS Observations of the King Edward Point Geodetic Observatory, South Georgia, South Atlantic Ocean

During February 2013 the King Edward Point (KEP) Geodetic Observatory was established in South Georgia, South Atlantic Ocean, through a University of Luxembourg funded research project and in collaboration with the United Kingdom’s National Oceanography Centre, British Antarctic Survey and Unavco, Inc. Due to its remote location in the South Atlantic Ocean, as well as, being one of few subaerial exposures of the Scotia plate, South Georgia Island has been a key location for a number of global monitoring networks, e.g. seismic, geomagnetic and oceanic. However, no geodetic monitoring station has been established, e.g. by the International Global Navigation Satellite System (GNSS) Service (IGS) community, despite the lack of such observations from this region. In this study we will present an evaluation of the GNSS observations from the KEP Geodetic Observatory for the period from February to August 2013. We calculate multipath and positioning statistics and compare these to those from IGS stations. The on-site meteorological data is compared to those from the nearby KEP meteorological station and global numerical weather models, and the impact of these data sets on delay and integrated water vapour estimates will be evaluated. We will discuss the installation in terms of its potential contributions to sea level observations using tide gauges and satellite altimetry, studies of tectonics, glacio-isostatic adjustment and atmospheric processes

Randomised controlled trial of intermittent vs continuous energy restriction during chemotherapy for early breast cancer

BACKGROUND: Excess adiposity at diagnosis and weight gain during chemotherapy is associated with tumour recurrence and chemotherapy toxicity. We assessed the efficacy of intermittent energy restriction (IER) vs continuous energy restriction (CER) for weight control and toxicity reduction during chemotherapy. METHODS: One hundred and seventy-two women were randomised to follow IER or CER throughout adjuvant/neoadjuvant chemotherapy. Primary endpoints were weight and body fat change. Secondary endpoints included chemotherapy toxicity, cardiovascular risk markers, and correlative markers of metabolism, inflammation and oxidative stress. RESULTS: Primary analyses showed non-significant reductions in weight (−1.1 (−2.4 to +0.2) kg, p = 0.11) and body fat (−1.0 (−2.1 to +0.1) kg, p = 0.086) in IER compared with CER. Predefined secondary analyses adjusted for body water showed significantly greater reductions in weight (−1.4 (−2.5 to −0.2) kg, p = 0.024) and body fat (−1.1 (−2.1 to −0.2) kg, p = 0.046) in IER compared with CER. Incidence of grade 3/4 toxicities were comparable overall (IER 31.0 vs CER 36.5%, p = 0.45) with a trend to fewer grade 3/4 toxicities with IER (18%) vs CER (31%) during cycles 4–6 of primarily taxane therapy (p = 0.063). CONCLUSIONS: IER is feasible during chemotherapy. The potential efficacy for weight control and reducing toxicity needs to be tested in future larger trials. CLINICAL TRIAL REGISTRATION: ISRCTN04156504

Consumer practices and prevalence of Campylobacter, Salmonella and norovirus in kitchens from six European countries

About 40% of foodborne infections are acquired in the home. The aim of the present study was to track contamination of pathogens during domestic food preparation and link the contamination to preparation practices. Research participants from 87 households in six European countries were observed and interviewed during shopping and preparation of a chicken and vegetable meal. The presence of Salmonella spp., Campylobacter spp. and norovirus on raw chicken, kitchen surfaces, cloths and sponges was determined. The prevalence of Campylobacter on raw chicken varied from 8.3% in Norway (NO) to 80% in France (FR) and Portugal (PT), with a mean prevalence of 57%. Campylobacter was found on half of the products that had been frozen and appeared to be less prevalent on chicken from supermarkets than other sources. Salmonella was found in 8.6% of raw chicken samples, exclusively from Hungary (HU). A relationship between observed practices and spread of pathogens to kitchen surfaces was found only for the use of cutting boards for chicken and/or vegetables. After food preparation, Campylobacter and Salmonella were isolated from 23% (samples derived from HU, RO, UK) and 8.7% (HU), respectively of cutting boards. Research participants in France and Portugal were more likely to buy products that fitted their recipe, with less need for using cutting boards. Using the same board and knife for vegetables after using it for chicken and without washing with detergent was common in Portugal and Romania, but not in the other countries. Contamination with Campylobacter to other kitchen surfaces or washing utensils were found in five households (UK, RO, PT). Rinsing chicken in sinks was common in three countries (PT, HU, RO), and washing vegetables in the same sink was also usual. Prevalence of Norovirus was low, with detection in one out of 451 samples. The participants' awareness of the risk posed by pathogens from raw chicken differed among the six countries, with higher awareness in Norway and the UK than the other countries studied. In conclusion, practices intended to avoid cross-contamination from chicken to kitchen surfaces and washing utensils are not established among consumers in all European countries. Nevertheless, cross-contamination events that disseminate infectious doses of pathogens seems to be rare, probably due to the relatively low levels of pathogens in food combined with food preferences. Food safety interventions must consider the national food culture, preferences, practices and the prevalence and levels of pathogens in food. Emphasis should be on providing and promoting chicken products with lower risk (prevalence of pathogens, ready-to-cook) and safe use of cutting boards

Priorities for protected area research

A hundred research priorities of critical importance to protected area management were identified by a targeted survey of conservation professionals; half researchers and half practitioners. Respondents were selected to represent a range of disciplines, every continent except Antarctica and roughly equal numbers of men and women. The results analysed thematically and grouped as potential research topics as by both practitioners and researchers. Priority research gaps reveal a high interest to demonstrate the role of protected areas within a broader discussion about sustainable futures and if and how protected areas can address a range of conservation and socio-economic challenges effectively. The paper lists the hundred priorities structured under broad headings of management, ecology, governance and social (including political and economic issues) and helps contribute to setting future research agendas

Priorities for protected area research

A hundred research priorities of critical importance to protected area management were identified by a targeted survey of conservation professionals; half researchers and half practitioners. Respondents were selected to represent a range of disciplines, every continent except Antarctica and roughly equal numbers of men and women. The results analysed thematically and grouped as potential research topics as by both practitioners and researchers. Priority research gaps reveal a high interest to demonstrate the role of protected areas within a broader discussion about sustainable futures and if and how protected areas can address a range of conservation and socio-economic challenges effectively. The paper lists the hundred priorities structured under broad headings of management, ecology, governance and social (including political and economic issues) and helps contribute to setting future research agendas.</p

Priorities for protected area research

CITATION: Dudley, N. et al. 2018. Priorities for protected area research. Parks, 24(1):35-50, doi:10.2305/IUCN.CH.2018.PARKS-24-1ND.en.The original publication is available at https://parksjournal.comA hundred research priorities of critical importance to protected area management were identified by a targeted survey of conservation professionals; half researchers and half practitioners. Respondents were selected to represent a range of disciplines, every continent except Antarctica and roughly equal numbers of men and women. The results analysed thematically and grouped as potential research topics as by both practitioners and researchers. Priority research gaps reveal a high interest to demonstrate the role of protected areas within a broader discussion about sustainable futures and if and how protected areas can address a range of conservation and socio-economic challenges effectively. The paper lists the hundred priorities structured under broad headings of management, ecology, governance and social (including political and economic issues) and helps contribute to setting future research agendas.Publisher's versio

Priorities for protected area research

A hundred research priorities of critical importance to protected area management were identified by a targeted survey of conservation professionals; half researchers and half practitioners. Respondents were selected to represent a range of disciplines, every continent except Antarctica and roughly equal numbers of men and women. The results analysed thematically and grouped as potential research topics as by both practitioners and researchers. Priority research gaps reveal a high interest to demonstrate the role of protected areas within a broader discussion about sustainable futures and if and how protected areas can address a range of conservation and socio-economic challenges effectively. The paper lists the hundred priorities structured under broad headings of management, ecology, governance and social (including political and economic issues) and helps contribute to setting future research agendas