Gamma Irradiation and Targeted Radionuclides Enhance the Expression of the Noradrenaline Transporter Transgene Controlled by the Radio-Inducible p21(WAF1/CIP1) Promoter

The use of radiation-inducible promoters to drive transgene expression offers the possibility of temporal and spatial regulation of gene activation. This study assessed the potential of one such promoter element, p21(WAF1/CIP1) (WAF1), to drive expression of the noradrenaline transporter (NAT) gene, which conveys sensitivity to radioiodinated meta-iodobenzylguanidine (MIBG). An expression vector containing NAT under the control of the radiation-inducible WAF1 promoter (pWAF/NAT) was produced. The non-NAT expressing cell lines UVW (glioma) and HCT116 (colorectal cancer) were transfected with this construct to assess radiation-controlled WAF1 activation of the NAT gene. Transfection of UVW and HCT cells with pWAF/NAT conferred upon them the ability to accumulate [(131)I]MIBG, which led to increased sensitivity to the radiopharmaceutical. Pretreatment of transfected cells with ? radiation or the radiopharmaceuticals [(123)I]MIBG or [(131)I]MIBG induced dose- and time-dependent increases in subsequent [(131)I]MIBG uptake and led to enhanced efficacy of [(131)I]MIBG-mediated cell kill. Gene therapy using WAF1-driven expression of NAT has the potential to expand the use of this therapeutic modality to tumors that lack a radio-targetable feature.

Rural Support Networks in the UK and Canada: The Influence of the Patrilineal Culture of Family Farming

Rural support organisations have emerged since agricultural restructuring of the 1980s. The paper draws on research from the UK and Canada to suggest that the support in both countries is derived from a patrilineal culture that still dominates family farming. The paper begins by outlining a conceptual basis for arguing that such a culture can be understood as comprising of male and female relational gender identities capable of explaining farm relationships, farm survival and adjustment strategies and community engagement. These components, it is argued, are facets of the patrilineal farming culture which must be understood if its impacts on all its members are to be appropriately comprehended and supported.

The paper has two key aims, therefore. Firstly it suggests that a more nuanced understanding of farming „culture? which is persistently patrilineal in nature is now required which is capable of addressing the realities of farming individuals?
lives as they perceive them. The conceptualisation of such a culture is informed
by drawing on insights from gender theory, agricultural geography and rural studies. This conceptual discussion provides the context for the paper?s second aim which is to demonstrate how rural support in both the UK and Canada is derived „from? and is influenced by such a patrilineal culture . Findings are
presented identifying five key themes from this conceptualization which influence the support of such organisations. Thus, it is suggested, that the nature of rural support can be better understood and the appropriateness of the support interrogated when such conceptualization is taken on board.

Ethics in neuroscience graduate training programs:Views and models from Canada

Consideration of the ethical, social, and policy implications of research has become increasingly important to scientists and scholars whose work focuses on brain and mind, but limited empirical data exist on the education in ethics available to them. We examined the current landscape of ethics training in neuroscience programs, beginning with the Canadian context specifically, to elucidate the perceived needs of mentors and trainees and offer recommendations for resource development to meet those needs. We surveyed neuroscientists at all training levels and interviewed directors of neuroscience programs and training grants. A total of 88% of survey respondents reported general interest in ethics, and 96% indicated a desire for more ethics content as it applies to brain research and clinical translation. Expert interviews revealed formal ethics education in over half of programs and in 90% of grants-based programs. Lack of time, resources, and expertise, however, are major barriers to expanding ethics content in neuroscience education. We conclude with an initial set of recommendations to address these barriers which includes the development of flexible, tailored ethics education tools, increased financial support for ethics training, and strategies for fostering collaboration between ethics experts, neuroscience program directors, and funding agencies. © 2010 the Authors. Journal Compilation © 2010 International Mind, Brain, and Education Society and Blackwell Publishing, Inc.

Family caregivers' ideal expectations of Canada's Compassionate Care Benefit

We present the findings of 57 interviews conducted in 2007-2008 with Canadians who have cared for a dying family member to examine their ideal expectations of the Compassionate Care Benefit (CCB) - a social programme providing job security and income support for workers caring for a dying person. Our aims are to (1) appreciate how intended users and other family caregivers view the programme's very nature; (2) identify programme challenges and improvements that emerge from considering family caregivers' ideal expectations; and (3) contribute to a larger evaluative study designed to make policy-relevant recommendations for CCB improvement. Review of transcripts across three respondent groups reveals four categories of ideal expectations: (1) eligibility, (2) informational, (3) timing and (4) financial. Ideal expectations were typically derived from respondents' experiences of care-giving, their knowledge of the programme and, for some, of applying for and/or receiving the CCB. Findings reveal that there are gaps between respondents' ideal expectations and their experienced realities. Such gaps may lead to disappointment being experienced by those who believe they should be eligible for the programme but are not, or should be entitled to receive some form of support that is not presently available. This analysis plays an important role in identifying potential changes for the CCB that may better support family caregivers, in that the ideal expectations serve as a starting point for articulating desirable programme amendments. This analysis also has wider relevance. For jurisdictions looking to create new social programmes to support caregivers based upon labour policy strategies and legislation, this analysis identifies considerations that should be made at the outset of development. For jurisdictions that already have employment-based caregiver support programmes, this analysis demonstrates that programme challenges may not always be met through legislative changes alone but also through measures such as increasing awareness. © 2011 Blackwell Publishing Ltd.

Canada's Compassionate Care Benefit:Is it an adequate public health response to addressing the issue of caregiver burden in end-of-life care?

Background: An increasingly significant public health issue in Canada, and elsewhere throughout the developed world, pertains to the provision of adequate palliative/end-of-life (P/EOL) care. Informal caregivers who take on the responsibility of providing P/EOL care often experience negative physical, mental, emotional, social and economic consequences. In this article, we specifically examine how Canada's Compassionate Care Benefit (CCB) - a contributory benefits social program aimed at informal P/EOL caregivers - operates as a public health response in sustaining informal caregivers providing P/EOL care, and whether or not it adequately addresses known aspects of caregiver burden that are addressed within the population health promotion (PHP) model. Methods. As part of a national evaluation of Canada's Compassionate Care Benefit, 57 telephone interviews were conducted with Canadian informal P/EOL caregivers in 5 different provinces, pertaining to the strengths and weaknesses of the CCB and the general caregiving experience. Interview data was coded with Nvivo software and emerging themes were identified by the research team, with such findings published elsewhere. The purpose of the present analysis was identified after comparing the findings to the literature specific to caregiver burden and public health, after which data was analyzed using the PHP model as a guiding framework. Results: Informal caregivers spoke to several of the determinants of health outlined in the PHP model that are implicated in their burden experience: gender, income and social status, working conditions, health and social services, social support network, and personal health practises and coping strategies. They recognized the need for improving the CCB to better address these determinants. Conclusions: This study, from the perspective of family caregivers, demonstrates that the CCB is not living up to its full potential in sustaining informal P/EOL caregivers. Effort is required to transform the CCB so that it may fulfill the potential it holds for serving as one public health response to caregiver burden that forms part of a healthy public policy that addresses the determinants of this burden. © 2011 Williams et al; licensee BioMed Central Ltd.

The influence of culture on home-based family caregiving at end-of-life: A case study of Dutch reformed family care givers in Ontario, Canada

Families are facing increased pressure to provide care to their terminally-ill or dying kin in the home. It is known that balancing care with other personal and social roles can adversely affect family caregivers' (FCGs) health, yet access to supportive services which can mitigate burden is often inadequate. Cultural factors are known to shape the experience of caregiving; however, most research to date tends to neglect the experiences of FCGs from different cultural groups. This understanding is necessary to ensure that supportive services are both meaningful and culturally-appropriate. Using qualitative methods, we undertook longitudinal research with a sample of Dutch Reformed FCGs (n = 5) to understand their experiences of caregiving and bereavement. The results of the study are suggestive of a cultural specificity with respect to caregiving that impacts both responsibilities and reactions to care. Three themes were salient to this group as a cultural entity: cultural attitudes towards care, religious beliefs and coping, and c. ulturally-informed care-seeking behaviours. These three themes were seen to be a function of their religious and ethnic identities and were reinforced by ties to the communities in which they resided. Cultural identity provided a framework through which to understand and make sense of the experience, while group membership provided access to networks of informal support. This research contributes to the geographical literature on care/caregiving by providing insight into the social, cultural and religious context of informal family caregiving with a population who live in close geographic proximity. On a practical level, this case study indicates the importance of considering how these factors may operate in other settings in order to implement timely and appropriate interventions to better support FCGs who are caring for their terminally-ill loved-ones at home.

Educating families about end-of-life care in advanced dementia:Acceptability of a Canadian family booklet to nurses from Canada, France, and Japan

Background: The families of people with late-stage dementia need to be informed about the course of the dementia and the comfort/ palliative care option. A booklet was written for that purpose and can be provided to family members by physicians and nurses. Methods: The acceptability of the booklet for nurses was tested in Canada (French and English version), France (French Canadian version) and Japan (translated and adapted version). Results: Overall, 188 nurses completed a survey questionnaire. The booklet was accepted best in Canada and less so in France and Japan. Despite regional variation, the majority of the nurses perceived the booklet as useful for families. The French and Japanese nurses also reported a greater need for palliative care education in advanced dementia. Conclusion: The booklet may help nurses educate families about end-of-life issues in dementia palliative care, but local adaptation of the booklet content and physician engagement are necessary.

GIANT LOBES OF CENTAURUS A RADIO GALAXY OBSERVED WITH THE SUZAKU X-RAY SATELLITE

We report on Suzaku observations of selected regions within the southern giant lobe of the radio galaxy Centaurus A. In our analysis we focus on distinct X-ray features detected with the X-ray Imaging Spectrometer within the range 0.5-10 keV, some of which are likely associated with fine structure of the lobe revealed by recent high-quality radio intensity and polarization maps. With the available photon statistics, we find that the spectral properties of the detected X-ray features are equally consistent with thermal emission from hot gas with temperatures kT > 1 keV, or with a power-law radiation continuum characterized by photon indices Gamma similar to 2.0 +/- 0.5. However, the plasma parameters implied by these different models favor a synchrotron origin for the analyzed X-ray spots, indicating that a very efficient acceleration of electrons up to greater than or similar to 10 TeV energies is taking place within the giant structure of Centaurus A, albeit only in isolated and compact regions associated with extended and highly polarized radio filaments. We also present a detailed analysis of the diffuse X-ray emission filling the whole field of view of the instrument, resulting in a tentative detection of a soft excess component best fitted by a thermal model with a temperature of kT similar to 0.5 keV. The exact origin of the observed excess remains uncertain, although energetic considerations point to thermal gas filling the bulk of the volume of the lobe and mixed with the non-thermal plasma, rather than to the alternative scenario involving a condensation of the hot intergalactic medium around the edges of the expanding radio structure. If correct, this would be the first detection of the thermal content of the extended lobes of a radio galaxy in X-rays. The corresponding number density of the thermal gas in such a case is n(g) similar to 10(-4) cm(-3), while its pressure appears to be in almost exact equipartition with the volume-averaged non-thermal pressure provided by the radio-emitting electrons and the lobes' magnetic field. A prominent large-scale fluctuation of the Galactic foreground emission, resulting in excess foreground X-ray emission aligned with the lobe, cannot be ruled out. Although tentative, our findings potentially imply that the structure of the extended lobes in active galaxies is likely to be highly inhomogeneous and non-uniform, with magnetic reconnection and turbulent acceleration processes continuously converting magnetic energy to internal energy of the plasma particles, leading to possibly significant spatial and temporal variations in the plasma beta parameter around the volume-averaged equilibrium condition beta similar to 1.

Stochastic particle acceleration in the lobes of giant radio galaxies

We investigate the acceleration of particles by Alfven waves via the second-order Fermi process in the lobes of giant radio galaxies. Such sites are candidates for the accelerators of ultra-high-energy cosmic rays (UHECR). We focus on the nearby Fanaroff-Riley type I radio galaxy Centaurus A. This is motivated by the coincidence of its position with the arrival direction of several of the highest energy Auger events. The conditions necessary for consistency with the acceleration time-scales predicted by quasi-linear theory are reviewed. Test particle calculations are performed in fields which guarantee electric fields with no component parallel to the local magnetic field. The results of quasi-linear theory are, to an order of magnitude, found to be accurate at low turbulence levels for non-relativistic Alfven waves and at both low and high turbulence levels in the mildly relativistic case. We conclude that for pure stochastic acceleration via Alfven waves to be plausible as the generator of UHECR in Cen A, the baryon number density would need to be several orders of magnitude below currently held upper limits.

Novel Radio Link Buffer Management Schemes for End-User Multi-class Traffic in High Speed Packet Access Networks

The requirement to provide multimedia services with QoS support in mobile networks has led to standardization and deployment of high speed data access technologies such as the High Speed Downlink Packet Access (HSDPA) system. HSDPA improves downlink packet data and multimedia services support in WCDMA-based cellular networks. As is the trend in emerging wireless access technologies, HSDPA supports end-user multi-class sessions comprising parallel flows with diverse Quality of Service (QoS) requirements, such as real-time (RT) voice or video streaming concurrent with non real-time (NRT) data service being transmitted to the same user, with differentiated queuing at the radio link interface. Hence, in this paper we present and evaluate novel radio link buffer management schemes for QoS control of multimedia traffic comprising concurrent RT and NRT flows in the same HSDPA end-user session. The new buffer management schemes—Enhanced Time Space Priority (E-TSP) and Dynamic Time Space Priority (D-TSP)—are designed to improve radio link and network resource utilization as well as optimize end-to-end QoS performance of both RT and NRT flows in the end-user session. Both schemes are based on a Time-Space Priority (TSP) queuing system, which provides joint delay and loss differentiation between the flows by queuing (partially) loss tolerant RT flow packets for higher transmission priority but with restricted access to the buffer space, whilst allowing unlimited access to the buffer space for delay-tolerant NRT flow but with queuing for lower transmission priority. Experiments by means of extensive system-level HSDPA simulations demonstrates that with the proposed TSP-based radio link buffer management schemes, significant end-to-end QoS performance gains accrue to end-user traffic with simultaneous RT and NRT flows, in addition to improved resource utilization in the radio access network.

Differences in cancer awareness and beliefs between Australia, Canada, Denmark, Norway, Sweden and the UK (the International Cancer Benchmarking Partnership):Do they contribute to differences in cancer survival?

Background:There are wide international differences in 1-year cancer survival. The UK and Denmark perform poorly compared with other high-income countries with similar health care systems: Australia, Canada and Sweden have good cancer survival rates, Norway intermediate survival rates. The objective of this study was to examine the pattern of differences in cancer awareness and beliefs across these countries to identify where these might contribute to the pattern of survival.Methods:We carried out a population-based telephone interview survey of 19 079 men and women aged =50 years in Australia, Canada, Denmark, Norway, Sweden and the UK using the Awareness and Beliefs about Cancer measure.Results:Awareness that the risk of cancer increased with age was lower in the UK (14%), Canada (13%) and Australia (16%) but was higher in Denmark (25%), Norway (29%) and Sweden (38%). Symptom awareness was no lower in the UK and Denmark than other countries. Perceived barriers to symptomatic presentation were highest in the UK, in particular being worried about wasting the doctor's time (UK 34%; Canada 21%; Australia 14%; Denmark 12%; Norway 11%; Sweden 9%).Conclusion:The UK had low awareness of age-related risk and the highest perceived barriers to symptomatic presentation, but symptom awareness in the UK did not differ from other countries. Denmark had higher awareness of age-related risk and few perceived barriers to symptomatic presentation. This suggests that other factors must be involved in explaining Denmark's poor survival rates. In the UK, interventions that address barriers to prompt presentation in primary care should be developed and evaluated. © 2013 Cancer Research UK. All rights reserved.