Arsenic, mode of action at biologically plausible low doses : what are the implications for low dose cancer risk?

Arsenic is an established human carcinogen. However, there has been much controversy about the shape of the arsenic response curve, particularly at low doses. This controversy has been exacerbated by the fact that the  mechanism(s) of arsenic carcinogenesis are still unclear and because there are few satisfactory animal models for arsenic-induced carcinogenesis. Recent epidemiological studies have shown that the relative risk for cancer among populations exposed to ≤60 ppb As in their drinking water is often lower than the risk for the unexposed control population. We have found that treatment of human keratinocyte and fibroblast cells with 0.1 to 1 μM arsenite (As^III) also produces a low dose protective effect against oxidative stress and DNA damage. This response includes increased transcription, protein levels and enzyme activity of several base excision repair genes, including DNA polymerase β and DNA ligase I. At higher concentrations (> 10 μM), As induces down-regulation of DNA repair, oxidative DNA damage and apoptosis. This low dose adaptive (protective) response by a toxic agent is known as hormesis and is characteristic of many agents that induce oxidative stress. A mechanistic model for arsenic carcinogenesis based on these data would predict that the low dose risk for carcinogenesis should be sub-linear. The threshold dose where toxicity outweighs protection is hard to predict based on in vitro dose response data, but might be estimated if one could determine the form (metabolite) and concentration of arsenic responsible for changes in gene regulation in the target tissues.

There are always two sides to a story: the use of social dramas as a mode of data analysis in information systems

With the continually evolving social nature of information systems research there is a need to identify different “modes of analysis” (Myers, 1997) to uncover our understanding of the complex, messy and often chaotic nature of human factors. One suggested mode of analysis is that of social dramas, a tool developed in the anthropological discipline by Victor Turner. The use of social dramas also utilises the work by Goffman (1959; 1997) and enables the researcher to investigate events from the front stage, reporting obvious issues in systems implementation, and from the back stage, identifying the hidden aspects of systems implementation and the underpinning discourses. A case study exploring the social dramas involved in systems selection and implementation has been provided to support the use of this methodological tool.

Effect of low-dose mobile versus traditional epidural techniques on mode of delivery: a randomised controlled trial

Background

Epidural analgesia is the most effective labour pain relief but is associated with increased rates of instrumental vaginal delivery and other effects, which might be related to the poor motor function associated with traditional epidural. New techniques that preserve motor function could reduce obstetric intervention. We did a randomised controlled trial to compare low-dose combined spinal epidural and low-dose infusion (mobile) techniques with traditional epidural technique.
Methods

Between Feb 1, 1999, and April 30, 2000, we randomly assigned 1054 nulliparous women requesting epidural pain relief to traditional (n=353), low-dose combined spinal epidural (n=351), or low-dose infusion epidural (n=350). Primary outcome was mode of delivery, and secondary outcomes were progress of labour, efficacy of procedure, and effect on neonates. We obtained data during labour and interviewed women postnatally.
Findings

The normal vaginal delivery rate was 35·1% in the traditional epidural group, 42·7% in the low-dose combined spinal group (odds ratio 1·38 [95% CI 1·01–1·89]; p=0·04); and 42·9% in the low-dose infusion group (1·39 [1·01–1·90]; p=0·04). These differences were accounted for by a reduction in instrumental vaginal delivery. Overall, 5 min APGAR scores of 7 or less were more frequent with low-dose technique. High-level resuscitation was more frequent in the low-dose infusion group.

Community-based study on knowledge, attitude and practice on the mode of transmission, prevention and treatment of the Buruli ulcer in Ga West District, Ghana

Buruli ulcer disease (BUD), a devastating tropical disease caused by Mycobacterium ulcerans, occurs in more than 80% of the administrative districts of Ghana. To elucidate community perceptions and
understanding of the aetiology of BUD, attitudes towards Buruli patients and treatment-seeking behaviours, we conducted a survey with 504 heads of households and seven focus group discussions in Ga West District, Ghana. Although 67% of participants regarded BUD as a health problem, 53% did not know its cause. Sixteen per cent attributed the cause to drinking non-potable water, 8.1% mentioned poor personal hygiene or dirty surroundings, and 5.5% identified swimming or wading in ponds as a risk factor. About 5.2% thought that witchcraft and curses cause BUD, and 71.8% indicated that BU sufferers first seek treatment from herbalists and only refer to the hospital as a last resort. The main
reasons were prospects of prolonged hospital stay, cost of transport, loss of earnings and opportunity associated with parents attending their children’s hospitalization over extended period, delays in being
attended by medical staff, and not knowing the cause of the disease or required treatment. The level of acceptance of BUD sufferers was high in adults but less so in children. The challenge facing health workers is to break the vicious cycle of poor medical outcomes leading to poor attitudes to hospital treatment in the community. Because herbalists are often the first people consulted by those who contract the disease, they need to be trained in early recognition of the pre-ulcerative stage of Buruli lesions.

Mode of delivery and problems in subsequent births : a register-based study from Finland

Objective

The purpose of this study was to investigate the effects of delivery on problems in subsequent births.
Study design

This was a cohort study that used register data for 73,104 mothers who had their first birth from 1987 to 1989 and subsequent births from 1987 to1998. Three analyses were performed: (1) examination of second births by mode of delivery in the first birth, with adjustment for confounders, (2) same parameter, with exclusion of women with persistent problems, and (3) examination of third births for women with a first birth vaginal delivery.
Results

More complications and poorer infant outcome were found at later births when the first or second birth was by cesarean delivery than after a first spontaneous vaginal delivery, even when women with persistent problems were excluded. Women with instrument first births had a similar rate of complications in the second birth to women with spontaneous vaginal births, but some infant outcomes were poorer.
Conclusion

Problems that are subsequent to cesarean delivery are unlikely to be explained entirely by indications for cesarean delivery.

The mode of pheromone evolution: evidence from bark beetles

Sex and aggregation pheromones consist of species-specific blends of chemicals. The way in which different species’ blends have evolved has been the subject of some debate. Theoretical predictions suggest that differences between species have arisen not through the accruing of small changes, but through major shifts in chemical composition. Using data on the aggregation pheromones of 34 species of bark beetle from two genera, Dendroctonus and Ips, we investigated how the distributions of the chemical components of their pheromone blends mirror their phylogenetic relationships. We tested whether there were consistent patterns that could be used to help elucidate the mode of pheromone evolution. Although there were obvious differences in pheromone blends between the two genera, the differences between species within each genus followed a less clear phylogenetic pattern. In both genera, closely related species are just as different as more distantly related species. Within Dendroctonus, particularly, most chemical components were distributed randomly across the phylogeny. Indeed, for some chemicals, closely related species may actually be more different than would be expected from a random distribution of chemical components. This argues strongly against the idea of minor shifts in pheromone evolution. Instead, we suggest that, within certain phylogenetic constraints, pheromone evolution in bark beetles is characterized by large saltational shifts, resulting in sibling species being substantially phenotypically (i.e. pheromonally) different from one another, thus agreeing with theoretical predictions.

The mode of evolution of aggregation pheromones in Drosophila species

Aggregation pheromones are used by fruit flies of the genus Drosophila to assemble on breeding substrates, where they feed, mate and oviposit communally. These pheromones consist of species-specific blends of chemicals. Here, using a phylogenetic framework, we examine how differences among species in these pheromone blends have evolved. Theoretical predictions, genetic evidence, and previous empirical analysis of bark beetle species, suggest that aggregation pheromones do not evolve gradually, but via major, saltational shifts in chemical composition. Using pheromone data for 28 species of Drosophila we show that, unlike with bark beetles, the distribution of chemical components among species is highly congruent with their phylogeny, with closely related species being more similar in their pheromone blends than are distantly related species. This pattern is also strong within the melanogaster species group, but less so within the virilis species group. Our analysis strongly suggests that the aggregation pheromones of Drosophila exhibit a gradual, not saltational, mode of evolution. We propose that these findings reflect the function of the pheromones in the ecology of Drosophila, which does not hinge on species specificity of aggregation pheromones as signals.

Effect of tool speeds during friction stir lap welding on mode of fracture and fracture strength of Al 6060-T5 joints

Friction stir lap welding (FSLW) of an age hardened Al alloy and evaluations of how FS speeds affected hooking and how hooking and softening due to FS affected fracture strength of the lap welds have been conducted. It was found that increasing rotation speed and reducing welding speed (v) increased the stir zone size (AB-SZ) and also hook size (h), although a maximum value of h (hMax) reached. The features of hooks for the observed - AB-SZ-h relationships are presented and explained. It was found that when h increased to a value of ~ 0.9 mm (for the 3 mm alloy sheets), it started to invoke a significant effect on reducing fracture strength. Factors such as FS softening and insufficient joining, limited the fracture strength of the lap welds for small h values and these are presented and discussed.

Economic value of mitigation of plant invaders in a subsistence economy : incorporating labour as a mode of payment

This paper presents the analysis of a choice experiment designed to estimate willingness-to-pay (WTP) to mitigate damages caused by invasive plant species in a rural community of Nepal. In order to address the cash constraints problem in a subsistence economy, two payment attributes, labour contribution and membership fee, were included in the choice sets. The results reveal that rural farmers have significant WTP for forest management activities, in terms of both cash and labour contributions. The results also suggest that rural farmers value their time in this context at a different rate from the current wage rate.

Membrane nanotubes in myeloid cells in the adult mouse cornea represent a novel mode of immune cell interaction

Membrane nanotubes (MNTs) are newly discovered cellular extensions that are either blind-ended or can connect widely separated cells. They have predominantly been investigated in cultured isolated cells, however, previously we were the first group to demonstrate the existence of these structures in vivo in intact mammalian tissues. We previously demonstrated the frequency of both cell–cell or bridging MNTs and blind-ended MNTs was greatest between major histocompatibility complex (MHC) class II+ cells during corneal injury or TLR ligand-mediated inflammation. The present study aimed to further explore the dynamics of MNT formation and their size, presence in another tissue, the dura mater, and response to stress factors and an active local viral infection of the murine cornea. Confocal live cell imaging of myeloid-derived cells in inflamed corneal explants from Cx3cr1GFP and CD11ceYFP transgenic mice revealed that MNTs form de novo at a rate of 15.5 μm/min. This observation contrasts with previous studies that demonstrated that in vitro these structures originate from cell–cell contacts. Conditions that promote formation of MNTs include inflammation in vivo and cell stress due to serum starvation ex vivo. Herpes simplex virus-1 infection did not cause a significant increase in MNT numbers in myeloid cells in the cornea above that observed in injury controls, confirming that corneal epithelium injury alone elicits MNT formation in vivo. These novel observations extend the currently limited understanding of MNTs in live mammalian tissues.

What was web 2.0? Versions as the dominant mode of internet history

This paper explores Web 2.0 as the marker of a discourse about the nature and purpose of the internet in the recent past. It focuses on how Web 2.0 introduced to our thinking about the internet a discourse of versions. Such a discourse enables the telling of a ‘history’ of the internet which involves a complex interweaving of past, present and future, as represented by the additional versions which the introduction of Web 2.0 enabled. The paper concludes that the discourse of versions embodied in Web 2.0 obscures as much as it reveals, and suggests a new project based on investigations of the everyday memories of the internet by which individual users create their own histories of online technology.

Is a change in mode of travel to school associated with a change in overall physical activity levels in children? Longitudinal results from the SPEEDY study

Background
Children who use active modes of travel (walking or cycling) to school are more physically active than those who use passive (motorised) modes. However, less is known on whether a change in mode of travel to school is associated with a change in children’s physical activity levels. The purpose of this analysis was to investigate the association between change in mode of travel to school and change in overall physical activity levels in children.

Methods
Data from 812 9–10 year old British children (59% girls) who participated in the SPEEDY study were analysed. During the summer terms of 2007 and 2008 participants completed a questionnaire and wore an accelerometer for at least three days. Two-level multiple linear regression models were used to explore the association between change in usual mode of travel to school and change in objectively measured time spent in MVPA.

Results
Compared to children whose reported mode of travel did not change, a change from a passive to an active mode of travel was associated with an increase in daily minutes spent in MVPA (boys: beta 11.59, 95% CI 0.94 to 22.24; girls: beta 11.92, 95% CI 5.00 to 18.84). This increase represented 12% of boys’ and 13% of girls’ total daily time spent in MVPA at follow-up.

Conclusion
This analysis provides further evidence that promoting active travel to school may have a role in contributing to increasing physical activity levels in children.

The silent witness: art as a mode of representation of voices and visions of how,as a woman, I build borders and bridges in enacting my identit(ies)

Feminist theorists unveil how women negotiate their identities within complex entanglements of social constructs such as race, ethnicity, religious belief and practices, cultural tradition, and values. Feminist artists use subjective experiences that shape representation and performativity in empowering women to have a ‘voice’. In this paper, I focus on ‘breaking silences’ through series of my artworks (as part of my PhD research) that represent self-narratives as subjectivities of life experiences, contingencies, and cultural shifts through migration transitions as new ways of figuration and reflection on such issues. I look through discourses of gender differences, nomadic subjectivity, and new ways of figurations (Braidotti 2011, 10) and the affect theory (Gregg and Seigworth 2010), and the concept of giving ‘voice’ (Berlant 2011). Such discourses frame how I interrogate and represent my gendered identities.