Dietary, lifestyle and clinico-pathological factors associated with APC mutations and promoter methylation in colorectal cancers from the EPIC-Norfolk Study

The tumour suppressor APC is the most commonly altered gene in colorectal cancer (CRC). Genetic and epigenetic alterations of APC may therefore be associated with dietary and lifestyle risk factors for CRC. Analysis of APC mutations in the extended mutation cluster region (codons 1276-1556) and APC promoter 1A methylation was performed on 185 archival CRC samples collected from participants of the European Prospective Investigation into Cancer (EPIC)-Norfolk Study, with the aim of relating these to high quality seven-day dietary and lifestyle data collected prospectively. Truncating APC mutations (APC+) and promoter 1A methylation (PM+) were identified in 43% and 23% of CRCs analysed, respectively. Distal CRCs were more likely than proximal CRCs to be APC+ or PM+ (P = 0.04). APC+ CRCs were more likely to be moderately/well differentiated and microsatellite stable than APC- CRCs (P = 0.05 and 0.03). APC+ CRC cases consumed more alcohol than their counterparts (P = 0.01) and PM+ CRC cases consumed lower levels of folate and fibre (P = 0.01 and 0.004). APC+ or PM+ CRC cases consumedhigher levels of processed meat and iron from red meat and red meat products (P=0.007 and 0.006). Specifically, CRC cases harbouring GC to AT transition mutations consumed higher levels of processed meat (35 versus 24 g/day, P = 0.04) and iron from red meat and red meat products (0.8 versus 0.6 mg/day, P = 0.05). In a logistic regression model adjusted for age, sex and cigarette smoking status, each 19g/day (1SD) increment increase in processed meat consumption was associated with cases with GC to AT mutations (OR 1.68, 95% CI 1.03-2.75). In conclusion, APC+ and PM+ CRCs may be influenced by diet and GC to AT mutations in APC are associated with processed meat consumption, suggesting a mechanistic link with dietary alkylating agents, such as N-nitroso compounds.

Elevated levels of corticotrophin-releasing factor binding protein in the blood of patients suffering from arthritis and septicaemia and the presence of novel ligands in synovial fluid.

In view of the reported inflammatory effects of corticotrophin-releasing factor (CRF) and the associated regulatory elements in the gene of its binding protein (BP), we postulate that both BP as well as novel BP-ligands other than CRF may be involved in inflammatory disease. We have investigated BP in the blood of patients with arthritis and septicaemia and have attempted to identify CRF and other BP-ligands in synovial fluid. The BP was found to be significantly elevated in the blood of patients with rheumatoid arthritis and septicaemia. There was less BP-ligand and CRF in synovial fluid from patients with rheumatoid arthritis that from those with osteo- or psoriatic arthritis. There was at least 10-fold more BP-ligand than CRF in the fluid of all three groups of patients. A small amount of immunoreactive human (h)CRF, eluting in the expected position of CRF-41, was detected after high-pressure liquid chromatography of arthritic synovial fluid; however, the bulk of material with BP-ligand binding activity eluted earlier, suggesting that synovial fluid contained novel peptides that interacted with the BP. These results would suggest that the BP and its ligands could play an endocrine immunomodulatory role in inflammatory disease.

Assessing the impact of occupant behaviour on the electricity consumption for lighting and small power in office buildings

Lighting and small power will typically account for more than half of the total electricity consumption in an office building. Significant variations in electricity used by different tenants suggest that occupants can have a significant impact on the electricity demand for these end-uses. Yet current modelling techniques fail to represent the interaction between occupant and the building environment in a realistic manner. Understanding the impact of such behaviours is crucial to improve the methodology behind current energy modelling techniques, aiming to minimise the significant gap between predicted and in-use performance of buildings. A better understanding of the impact of occupant behaviour on electricity consumption can also inform appropriate energy saving strategies focused on behavioural change. This paper reports on a study aiming to assess the intent of occupants to switch off lighting and appliances when not in use in office buildings. Based on the Theory of Planned Behaviour, the assessment takes the form of a questionnaire and investigates three predictors to behaviour individually: 1) behavioural attitude; 2) subjective norms; 3) perceived behavioural control. The paper details the development of the assessment procedure and discusses preliminary findings from the study. The questionnaire results are compared against electricity consumption data for individual zones within a multi-tenanted office building. Initial results demonstrate a statistically significant correlation between perceived behavioural control and energy consumption for lighting and small power

The gender gap in real estate sales: negotiation skill or agent selection?

This study examines differences in net selling price for residential real estate across male and female agents. A sample of 2,020 home sales transactions from Fulton County, Georgia are analyzed in a two-stage least squares, geospatial autoregressive corrected, semi-log hedonic model to test for gender and gender selection effects. Although agent gender seems to play a role in naïve models, its role becomes inconclusive as variables controlling for possible price and time on market expectations of the buyers and sellers are introduced to the models. Clear differences in real estate sales prices, time on market, and agent incomes across genders are unlikely due to differences in negotiation performance between genders or the mix of genders in a two-agent negotiation. The evidence suggests an interesting alternative to agent performance: that buyers and sellers with different reservation price and time on market expectations, such as those selling foreclosure homes, tend to select agents along gender lines.

Source splitting via the point source method

We introduce a new algorithm for source identification and field splitting based on the point source method (Potthast 1998 A point-source method for inverse acoustic and electromagnetic obstacle scattering problems IMA J. Appl. Math. 61 119–40, Potthast R 1996 A fast new method to solve inverse scattering problems Inverse Problems 12 731–42). The task is to separate the sound fields uj, j = 1, ..., n of sound sources supported in different bounded domains G1, ..., Gn in from measurements of the field on some microphone array—mathematically speaking from the knowledge of the sum of the fields u = u1 + + un on some open subset Λ of a plane. The main idea of the scheme is to calculate filter functions , to construct uℓ for ℓ = 1, ..., n from u|Λ in the form We will provide the complete mathematical theory for the field splitting via the point source method. In particular, we describe uniqueness, solvability of the problem and convergence and stability of the algorithm. In the second part we describe the practical realization of the splitting for real data measurements carried out at the Institute for Sound and Vibration Research at Southampton, UK. A practical demonstration of the original recording and the splitting results for real data is available online.

The potential for community groups to promote sustainable living

In recent times there has been a growing recognition amongst policy-makers of the role for community-based action in contributing to the broader aims of energy policy and climate change. In this paper, we will examine the potential for existing community groups to use their influence and elements of internal cohesion to encourage more widespread understanding and adoption of sustainable lifestyle habits; both amongst their members and within the broader communities of which they are a part. Findings are presented from recent empirical work with a range of well-established community groups for whom environmental issues are not their main priority. A central aspect of the research was to explore both the current status and potential role of groups that may have the capacity to reach and influence a broader sphere of the public than energy/environment specific initiatives of recent times have been able to achieve. Representing a diversity of interests, age groups and functionality, the results suggest that the potential for more effective ‘bottom-up’ engagement on climate change and sustainable living might be given fresh impetus by these types of established community groups and their networks. An assessment of what motivates participation and membership in the groups highlights a series of factors common to all groups and a smaller number that are significant for particular groups individually. It is argued that an appreciation of motivating factors can be useful in understanding more clearly how such groups are able to survive and maintain cohesion over time. The findings also suggest that climate change action means different things for different groups, with the diversity of the groups bringing with it the challenge of making sustainable living relevant to a range of interests and different shared values.

The anti-epileptic drug Valproic Acid (VPA) inhibits steroidogenesis in bovine theca and granulosa cells in vitro

Valproic acid (VPA) is used widely to treat epilepsy and bipolar disorder. Women undergoing VPA treatment reportedly have an increased incidence of polycystic ovarian syndrome (PCOS)-like symptoms including hyperandrogenism and oligo- or amenorrhoea. To investigate potential direct effects of VPA on ovarian steroidogenesis we used primary bovine theca (TC) and granulosa (GC) cells maintained under conditions that preserve their 'follicular' phenotype. Effects of VPA (7.8-500 µg/ml) on TC were tested with/without LH. Effects of VPA on GC were tested with/without FSH or IGF analogue. VPA reduced (P<0.0001) both basal (70% suppression; IC(50) 67±10 µg/ml) and LH-induced (93% suppression; IC(50) 58±10 µg/ml) androstenedione secretion by TC. VPA reduced CYP17A1 mRNA abundance (>99% decrease; P<0.0001) with lesser effects on LHR, STAR, CYP11A1 and HSD3B1 mRNA (<90% decrease; P<0.05). VPA only reduced TC progesterone secretion induced by the highest (luteinizing) LH dose tested; TC number was unaffected by VPA. At higher concentrations (125-500 µg/ml) VPA inhibited basal, FSH- and IGF-stimulated estradiol secretion (P<0.0001) by GC without affecting progesterone secretion or cell number. VPA reversed FSH-induced upregulation of CYP19A1 and HSD17B1 mRNA abundance (P<0.001). The potent histone deacetylase (HDAC) inhibitors trichostatin A and scriptaid also suppressed TC androstenedione secretion and granulosal cell oestrogen secretion suggesting that the action of VPA reflects its HDAC inhibitory properties. In conclusion, these findings refute the hypothesis that VPA has a direct stimulatory action on TC androgen output. On the contrary, VPA inhibits both LH-dependent androgen production and FSH/IGF-dependent estradiol production in this in vitro bovine model, likely by inhibition of HDAC.

Spatio-temporal variation in predation by urban domestic cats (Felis catus) and the acceptability of possible management actions in the UK

Urban domestic cat (Felis catus) populations can attain exceedingly high densities and are not limited by natural prey availability. This has generated concerns that they may negatively affect prey populations, leading to calls for management. We enlisted cat-owners to record prey returned home to estimate patterns of predation by free-roaming pets in different localities within the town of Reading, UK and questionnaire surveys were used to quantify attitudes to different possible management strategies. Prey return rates were highly variable: only 20% of cats returned ≥4 dead prey annually. Consequently, approximately 65% of owners received no prey in a given season, but this declined to 22% after eight seasons. The estimated mean predation rate was 18.3 prey cat−1 year−1 but this varied markedly both spatially and temporally: per capita predation rates declined with increasing cat density. Comparisons with estimates of the density of six common bird prey species indicated that cats killed numbers equivalent to adult density on c. 39% of occasions. Population modeling studies suggest that such predation rates could significantly reduce the size of local bird populations for common urban species. Conversely, most urban residents did not consider cat predation to be a significant problem. Collar-mounted anti-predation devices were the only management action acceptable to the majority of urban residents (65%), but were less acceptable to cat-owners because of perceived risks to their pets; only 24% of cats were fitted with such devices. Overall, cat predation did appear to be of sufficient magnitude to affect some prey populations, although further investigation of some key aspects of cat predation is warranted. Management of the predation behavior of urban cat populations in the UK is likely to be challenging and achieving this would require considerable engagement with cat owners.