Dispatches from the Front: The Life of Matthew Halton, Canada’s Voice at War (Book Review) by David Halton

Review of Dispatches from the Front: The Life of Matthew Halton, Canada’s Voice at War by Matthew Halto

Transport proteins determine drug sensitivity and resistance in a protozoan parasite, Trypanosoma brucei

Drug resistance in pathogenic protozoa is very often caused by changes to the ‘transportome’ of the parasites. In Trypanosoma brucei, several transporters have been implicated in uptake of the main classes of drugs, diamidines and melaminophenyl arsenicals. The resistance mechanism had been thought to be due to loss of a transporter known to carry both types of agents: the aminopurine transporter P2, encoded by the gene TbAT1. However, although loss of P2 activity is well-documented as the cause of resistance to the veterinary diamidine diminazene aceturate (Berenil®), cross-resistance between the human-use arsenical melarsoprol and the diamidine pentamidine (MPXR) is the result of loss of a separate High Affinity Pentamidine Transporter (HAPT1). A genome-wide RNAi library screen for resistance to pentamidine, published in 2012, gave the key to the genetic identity of HAPT1 by linking the phenomenon to a locus that contains the closely related T. brucei aquaglyceroporin genes TbAQP2 and TbAQP3. Further analysis determined that knockdown of only one pore, TbAQP2, produced the MPXR phenotype. TbAQP2 is an unconventional aquaglyceroporin with unique residues in the “selectivity region” of the pore, and it was found that in several MPXR lab strains the WT gene was either absent or replaced by a chimeric protein, recombined with parts of TbAQP3. Importantly, wild-type AQP2 was also absent in field isolates of T. b. gambiense, correlating with the outcome of melarsoprol treatment. Expression of a wild-type copy of TbAQP2 in even the most resistant strain completely reversed MPXR and re-introduced HAPT1 function and transport kinetics. Expression of TbAQP2 in Leishmania mexicana introduced a pentamidine transport activity indistinguishable from HAPT1. Although TbAQP2 has been shown to function as a classical aquaglyceroporin it is now clear that it is also a high affinity drug transporter, HAPT1. We discuss here a possible structural rationale for this remarkable ability

A wireless sensor network system deployment for detecting stick slip motion in glaciers

The behaviour of glaciers is an area in which only limited research has been carried out due to the difficulties of monitoring sub-glacial movements. The authors believe that this can be addressed by the deployment of a wireless sensor network, consisting of heterogeneous sensors to instrument this activity. By deploying a sensor network measurements can be taken for a longer period than would otherwise be possible. The initial designs for this sensor network are presented along with details of some of the challenges posed by the project

It's what's expected: genetic testing for inherited conditions, CHERE Discussion Paper No 46

The development of new genetic technology brings with it responsibility for evaluating the effectiveness and efficiency of testing programs, including gaining an understanding of the value of information. This study examined the factors individuals took into account when making decisions about having a genetic test for Tay Sachs Disease. Fifteen people participated in an in-depth interview as they attended a clinic for genetic testing. A thematic analysis of the data was undertaken. Participants were most influenced to have testing by personal factors: e.g. ethnic background and desire to have children. Disease characteristics were also important. The results informed the development of a Stated Preference Discrete Choice (SPDCM) experiment. Participants were motivated to have testing by a need for reassurance and certainty. Thus, information was an important outcome for them. The results of the SPDCM experiment indicate that participants valued information positively thus providing support for the findings of the qualitative research.Genetic testing, Tay Sachs disease, Discrete choice experiment

Expert views of peer-based interventions for prisoner health.

Purpose: Formalised support services for prisoners that rely on peer methods of delivery show promising health and social outcomes but there is also conjecture that negative effects, both at an individual and organisational level, can occur. Design/methodology/approach: Individuals with recognised professional expertise from various sectors (including ex-prisoners) were invited to contribute to an expert symposium to share their perceptions of the positive and negative effects of peer interventions in prison. Discussions and debate were audio recorded with the consent of all delegates and verbatim transcripts were analysed using Framework Analysis. Findings: According to the participants, peer interventions in the prison setting created both positive and negative impacts. It was clear from the evidence gathered that peer interventions in prisons can impact positively on health outcomes, but these effects were perceived to be more well-defined for peer deliverers. The notion that peer deliverers can be subjected to ‘burnout’ suggests that supervisory processes for peer workers need to be considered carefully in order to avoid the intervention from being counter-productive. Organizationally, one of the salient issues was the adverse effects that peer interventions cause to the security of the prison. Originality/value: To our knowledge, this is the first time an expert symposium has been conducted to specifically examine peer interventions in prison and to consider the effects, both positive and negative, of such schemes

Haunted houses: influence and the creative process in Virginia Woolf's novels

This thesis argues that rather than being an innovative, modernist writer, Virginia Woolfs methods, themes, and aspirations were conservative in certain central ways, for her novels were influenced profoundly by the work of writers from earlier eras. This argument is developed both by demonstrating that Woolf was influenced by other writers, and also by exploring the dynamics of how this process of influence took place. The thesis contends that this process included identification with past writers and a longing for the literary past, which complicated Woolfs attempts to negotiate the past and its values. After a chapter examining theoretical approaches to the concept of literary influence, the thesis makes a detailed study of Woolf's engagement with her influences in eight of her novels. Woolf s responses to influence are divided into three phases. In the first phase, up to the mid- 1920s, she wrestled with existing perceptions of the woman writer as she looked to female precursors as role models and struggled with their legacies. At the same time, she sought refuge from such a problematic inheritance by turning to her male precursors to try and gain covert access to the literary traditions which were thought to be the birthright of the men of her generation. In the second phase of her career, in the late 1920s, Woolf continued to deal with the absence of a ready-made tradition by elegizing writers she had known and the literary traditions they represented. In the process of mourning other writers, it is suggested, Woolf remade them in her imagination to be like herself. This process of identification continued in the third phase, in The Naves and Between the Acts, when Woolf drew on the work of Wordsworth and Coleridge, respectively, to explore and develop her mature identity as a writer

Quantifying the implicit process flow abstraction in SBGN-PD diagrams with Bio-PEPA

For a long time biologists have used visual representations of biochemical networks to gain a quick overview of important structural properties. Recently SBGN, the Systems Biology Graphical Notation, has been developed to standardise the way in which such graphical maps are drawn in order to facilitate the exchange of information. Its qualitative Process Diagrams (SBGN-PD) are based on an implicit Process Flow Abstraction (PFA) that can also be used to construct quantitative representations, which can be used for automated analyses of the system. Here we explicitly describe the PFA that underpins SBGN-PD and define attributes for SBGN-PD glyphs that make it possible to capture the quantitative details of a biochemical reaction network. We implemented SBGNtext2BioPEPA, a tool that demonstrates how such quantitative details can be used to automatically generate working Bio-PEPA code from a textual representation of SBGN-PD that we developed. Bio-PEPA is a process algebra that was designed for implementing quantitative models of concurrent biochemical reaction systems. We use this approach to compute the expected delay between input and output using deterministic and stochastic simulations of the MAPK signal transduction cascade. The scheme developed here is general and can be easily adapted to other output formalisms

Do two rights fix a wrong? A study of employee and organizational responses to abusive supervision in New Zealand

Organizational justice theories suggest that employees who are abused by their supervisor are likely to respond with lower job and personal outcomes. However, an under-explored area has been the influence of support perceptions. The present study suggests that perceived supervisor support (PSS) and perceived organizational support (POS) may moderate the influence of abusive supervision, and this was tested with three-way interactions. Data was collected from two samples: (1) 100 blue-collar workers in construction and (2) 218 random Maori employees from a variety of industries and professions. Structural equation modeling confirmed the unique constructs of the study measures towards abusive supervision and PSS and POS. Direct effects showed abusive supervision was significant and negative in both samples towards life satisfaction, job satisfaction, and organizational-based self-esteem (OBSE), and significant and positive in both samples towards turnover intentions, anxiety, depression, and insomnia. The results indicated that abusive supervision accounted for large amounts of variance towards all outcomes, with the exception of life satisfaction in study two (7%), and insomnia (8% in study one, and 4% in study two), ranging from 13%-32% variance. Significant three-way interactions were found for all outcomes except turnover intentions and insomnia. The three-way interaction towards life satisfaction in study one indicated that under abusive supervision, respondents with high PSS and high POS experienced the greatest levels of life satisfaction. Similar relationships were found toward depression (study one and two) and anxiety (study one), showing that respondents who experienced high abusive supervision, high PSS, and high POS had the lowest levels of negative mental health outcomes amongst all abused respondents. This suggested a potentially cumulative effect of multiple sources of support. Furthermore, towards job satisfaction in study two, findings show respondents with high abusive supervision and high POS reported the highest job satisfaction, irrespective of levels of PSS. A similar relationship was found toward OBSE in study two, suggesting that of the support variables examined, POS may have greater effect on outcomes, thereby supporting research of Dawley, Andrews and Bucklew (2008) who found POS to be the best predictor of organizational outcomes. Overall, this paper supports the notion that perceptions of support may moderate the influence of abusive supervision perceptions on employee’s work and personal outcomes. The findings show that while abusive supervision can play a dominant role on outcomes, this can be somewhat nullified by greater support from the organization. This has strong implications for firms dealing with problem supervisors, signaling the importance of establishing POS, and emphasizing that creating a supportive organization may be the first step to enabling employees to develop positive work and individual outcomes