Persistent Organic Pollutants (POPs) and inorganic elements in predatory bird livers and eggs 2007 to 2009: a Predatory Bird Monitoring Scheme (PBMS) Report

The Predatory Bird Monitoring Scheme (PBMS; http://pbms.ceh.ac.uk/) is the umbrella project that encompasses the Centre for Ecology & Hydrology’s National Capability contaminant monitoring and surveillance work on avian predators. By monitoring sentinel vertebrate species, the PBMS aims to detect and quantify current and emerging chemical threats to the environment and in particular to vertebrate wildlife. Sparrowhawk livers were analysed for a range of persistent organic pollutants (POPs) and heavy metals. Sparrowhawks are studied because they have a wide distribution across the Britain and can be used as a sentinel species for the terrestrial environment. Mean PCB and mercury liver concentrations were below those thought to have an adverse effect on individual birds. Pollutants, such as mercury and PCBs, can affect development and hatchability. Therefore, the PBMS also monitors the levels of contaminants in the eggs of a range of species including those of conservation concern, such as golden eagle and the re-introduced white-tailed sea eagle. Other species that are monitored are the northern gannet, which is used as a monitor of the marine environment, and merlin that hunts in upland habitats. The residues measured in the eggs of golden eagle and gannets collected between 2007 and 2009 were below those thought to have an adverse effect, but some residues in individual merlin eggs were above concentrations suggested to be indicative of no effect concentrations for birds generally. Few white-tailed see eagle eggs are received for analysis by the PBMS but many of the eggs that have been analysed, including one of the eggs analysed for this report, have DDE, PCB and/or mercury concentrations above levels associated with adverse effects on bird embryos and hatching success. In terms of long-term trends, there has been a decline in congener sum PCB contamination in the eggs of most of the species that have been monitored, except for coastal nesting golden eagles. In contrast however, there has been no significant decline over time in PCB concentrations in sparrowhawk livers and concentrations of ‘Paris 10’ congener sum and PCB-TEQ concentrations have also largely remained unchanged in both livers and eggs since monitoring began in 1996. Evidence for changes over time in mercury concentrations in predatory birds or their eggs is inconsistent across the species monitored. Where a decline has been detected, it has occurred before approximately 1990 and remained largely unchanged since then

LexOPS: An R package and user interface for the controlled generation of word stimuli

LexOPS is an R package and user interface designed to facilitate the generation of word stimuli for use in research. Notably, the tool permits the generation of suitably controlled word lists for any user-specified factorial design and can be adapted for use with any language. It features an intuitive graphical user interface, including the visualization of both the distributions within and relationships among variables of interest. An inbuilt database of English words is also provided, including a range of lexical variables commonly used in psycholinguistic research. This article introduces LexOPS, outlining the features of the package and detailing the sources of the inbuilt dataset. We also report a validation analysis, showing that, in comparison to stimuli of existing studies, stimuli optimized with LexOPS generally demonstrate greater constraint and consistency in variable manipulation and control. Current instructions for installing and using LexOPS are available at https://JackEdTaylor.github.io/LexOPSdocs/

Progressive resistance training and stretching following surgery for breast cancer: study protocol for a randomised controlled trial

BACKGROUND: Currently 1 in 11 women over the age of 60 in Australia are diagnosed with breast cancer. Following treatment, most breast cancer patients are left with shoulder and arm impairments which can impact significantly on quality of life and interfere substantially with activities of daily living. The primary aim of the proposed study is to determine whether upper limb impairments can be prevented by undertaking an exercise program of prolonged stretching and resistance training, commencing soon after surgery. METHODS/DESIGN: We will recruit 180 women who have had surgery for early stage breast cancer to a multicenter single-blind randomized controlled trial. At 4 weeks post surgery, women will be randomly assigned to either an exercise group or a usual care (control) group. Women allocated to the exercise group will perform exercises daily, and will be supervised once a week for 8 weeks. At the end of the 8 weeks, women will be given a home-based training program to continue indefinitely. Women in the usual care group will receive the same care as is now typically provided, i.e. a visit by the physiotherapist and occupational therapist while an inpatient, and receipt of pamphlets. All subjects will be assessed at baseline, 8 weeks, and 6 months later. The primary measure is arm symptoms, derived from a breast cancer specific questionnaire (BR23). In addition, range of motion, strength, swelling, pain and quality of life will be assessed. DISCUSSION: This study will determine whether exercise commencing soon after surgery can prevent secondary problems associated with treatment of breast cancer, and will thus provide the basis for successful rehabilitation and reduction in ongoing problems and health care use. Additionally, it will identify whether strengthening exercises reduce the incidence of arm swelling. TRIAL REGISTRATION: The protocol for this study is registered with the Australian Clinical Trials Registry (ACTRN012606000050550)

ASCT2/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer

Alanine, serine, cysteine-preferring transporter 2 (ASCT2; SLC1A5) mediates uptake of glutamine, a conditionally essential amino acid in rapidly proliferating tumour cells. Uptake of glutamine and subsequent glutaminolysis is critical for activation of the mTORC1 nutrient-sensing pathway, which regulates cell growth and protein translation in cancer cells. This is of particular interest in breast cancer, as glutamine dependence is increased in high-risk breast cancer subtypes. Pharmacological inhibitors of ASCT2-mediated transport significantly reduced glutamine uptake in human breast cancer cell lines, leading to the suppression of mTORC1 signalling, cell growth and cell cycle progression. Notably, these effects were subtype-dependent, with ASCT2 transport critical only for triple-negative (TN) basal-like breast cancer cell growth compared with minimal effects in luminal breast cancer cells. Both stable and inducible shRNA-mediated ASCT2 knockdown confirmed that inhibiting ASCT2 function was sufficient to prevent cellular proliferation and induce rapid cell death in TN basal-like breast cancer cells, but not in luminal cells. Using a bioluminescent orthotopic xenograft mouse model, ASCT2 expression was then shown to be necessary for both successful engraftment and growth of HCC1806 TN breast cancer cells in vivo. Lower tumoral expression of ASCT2 conferred a significant survival advantage in xenografted mice. These responses remained intact in primary breast cancers, where gene expression analysis showed high expression of ASCT2 and glutamine metabolism-related genes, including GLUL and GLS, in a cohort of 90 TN breast cancer patients, as well as correlations with the transcriptional regulators, MYC and ATF4. This study provides preclinical evidence for the feasibility of novel therapies exploiting ASCT2 transporter activity in breast cancer, particularly in the high-risk basal-like subgroup of TN breast cancer where there is not only high expression of ASCT2, but also a marked reliance on its activity for sustained cellular proliferation

Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial

© Cuzick et al. Open Access article distributed under the terms of CC BY.http://dx.doi.org/10.1016/S1470-2045(14)71171-

Effect of incentives on insecticide-treated bed net use in sub-Saharan Africa: a cluster randomized trial in Madagascar

<p>Abstract</p> <p>Background</p> <p>Insecticide-treated bed nets (ITNs) have been shown to reduce morbidity and mortality due to malaria in sub-Saharan Africa. Strategies using incentives to increase ITN use could be more efficient than traditional distribution campaigns. To date, behavioural incentives have been studied mostly in developed countries. No study has yet looked at the effect of incentives on the use of ITNs. Reported here are the results of a cluster randomized controlled trial testing household-level incentives for ITN use following a free ITN distribution campaign in Madagascar.</p> <p>Methods</p> <p>The study took place from July 2007 until February 2008. Twenty-one villages were randomized to either intervention or control clusters. Households in both clusters received a coupon redeemable for one ITN. After one month, intervention households received a bonus for ITN use, determined by visual confirmation of a mounted ITN. Data were collected at baseline, one month and six months. Both unadjusted and adjusted results, using cluster specific methods, are presented.</p> <p>Results</p> <p>At baseline, 8.5% of households owned an ITN and 6% were observed to have a net mounted over a bed in the household. At one month, there were no differences in ownership between the intervention and control groups (99.5% vs. 99.4%), but net use was substantially higher in the intervention group (99% vs. 78%), with an adjusted risk ratio of 1.24 (95% CI: 1.10 to 1.40; p < 0.001). After six months, net ownership had decreased in the intervention compared to the control group (96.7% vs. 99.7%), with an adjusted risk ratio of 0.97 (p < 0.01). There was no difference between the groups in terms of ITN use at six months; however, intervention households were more likely to use a net that they owned (96% vs. 90%; p < 0.001).</p> <p>Conclusions</p> <p>Household-level incentives have the potential to significantly increase the use of ITNs in target households in the immediate-term, but, over time, the use of ITNs is similar to households that did not receive incentives. Providing incentives for behaviour change is a promising tool that can complement traditional ITN distribution programmes and improve the effectiveness of ITN programmes in protecting vulnerable populations, especially in the short-term.</p

A phase I study of extended dosing with lomeguatrib with temozolomide in patients with advanced melanoma

Lomeguatrib, an O6-methylguanine-DNA methyltransferase inactivator, was evaluated in an extended dosing regimen with temozolomide, designed according to pharmacodynamic data from previous studies. Patients with unresectable stage 3 or 4 cutaneous or unknown primary melanoma metastases were treated with lomeguatrib 40 mg, b.i.d. for 10 or 14 days and temozolomide 75–100 mg m−2 on days 1–5. Drugs were administered orally with cycles repeated every 28 days, for up to six cycles. A total of 32 patients were recruited to the study. Lomeguatrib for 10 days with temozolomide 75 mg m−2 was established as the optimal extended lomeguatrib dosing schedule, with haematological toxicity being dose limiting. There were two partial responses to treatment giving an overall response rate of 6.25%. Extending lomeguatrib administration beyond that of temozolomide requires a reduced dose of the latter agent. Only limited clinical activity was seen, suggesting no advantage for this regimen over conventional temozolomide administration in the treatment of melanoma