Variation in offspring size towards the high elevational range edge of a montane annual

Understanding the ecological determinants of species’ distribution is a fundamental goal of ecology, and is increasingly important with changing limits to species’ range. Species often reach distributional limits on gradients of resource availability, but the extent to which offspring provisioning varies towards range limits is poorly understood. Selection is generally expected to favour higher provisioning of individual offspring in environments with short growing seasons and limited moisture, nutrients, or hosts for parasitism. However, individual provisioning may decline if parent size is limited by resources. This thesis focuses on three major questions: 1) does seed size vary over an elevational gradient? 2) does this variation respond adaptively towards the range limit? and 3) is potential elevational variation environmentally or genetically controlled? I tested variation in seed investment towards the upper elevational limit of the hemiparasitic annual herb Rhinanthus minor, sampled across an elevational range of 1,000m in the Rocky Mountains of Alberta, Canada. I also used a reciprocal transplant experiment to address the heritability of seed mass. Seed mass increased marginally towards higher elevations, while seed number and plant size declined. There was a strong elevational increase in seed mass scaled by overall plant size. Therefore, investment in individual seeds was higher towards the upper range edge, indicating potential adaptation of the reproductive strategy to allow for establishment in marginal environments. Genetic, environmental, and genotype-by-environment interactions were observed in transplanted populations, but the relative proportions of these effects on seed size were unclear.

Association of functional haem oxygenase-1 gene promoter polymorphism with polycystic kidney disease and IgA nephropathy

Background: Haem oxygenase-1 (HO-1) is a cytoprotective molecule that is reported to have a protective role in a variety of experimental models of renal injury. A functional dinucleotide repeat (GT)n polymorphism, within the HO-1 promoter, regulates HO-1 gene expression; a short number of repeats (S-allele <25) increases transcription. We report the first assessment of the role of this HO-1 gene promoter polymorphism in chronic kidney disease due to autosomal dominant polycystic kidney disease (ADPKD) and IgA nephropathy (IgAN).

Methods: The DNA from 160 patients (99% Caucasian) on renal replacement therapy (RRT) was genotyped. The primary renal disease was ADPKD in 100 patients and biopsy-proven IgAN in 60 patients.

Results: Overall, the mean age at commencement of RRT was not significantly different between patients with and without an S-allele (44.1 years versus 45.0 years, P = 0.64). In patients with ADPKD, the age at commencement of RRT was comparable regardless of the HO-1 genotype (47.7 years versus 46.7 years, P = 0.59). The same was true in patients with IgAN (38.3 years versus 42.2 years, P = 0.28).

Conclusion: This suggests that the functional HO-1 promoter polymorphism does not influence renal survival in CKD due to ADPKD or IgAN.

Habitat for Humanity: Calibrating Best Practice Against the MDGs

Poverty alleviation lies at the heart of contemporary international initiatives on development. The key to development is the creation of an environment in which people can develop their potential, leading productive, creative lives in accordance with their needs, interests and faith. This entails, on the one hand, protecting the vulnerable from things that threaten their survival, such as inadequate nutrition, disease, conflict, natural disasters and the impact of climate change, thereby enhancing the poor’s capabilities to develop resilience in difficult conditions. On the other hand, it also requires a means of empowering the poor to act on their own behalf, as individuals and communities, to secure access to resources and the basic necessities of life such as water, food, shelter, sanitation, health and education. ‘Development’, from this perspective, seeks to address the sources of human insecurity, working towards ‘freedom from want, freedom from fear’ in ways that empower the vulnerable as agents of development (not passive recipients of benefaction).

Recognition of the magnitude of the problems confronted by the poor and failure of past interventions to tackle basic issues of human security led the United Nations (UN) in September 2000 to set out a range of ambitious, but clearly defined, development goals to be achieved by 2015. These are known as the Millennium Development Goals (MDGs). The intention of the UN was to mobilise multilateral international organisations, non-governmental organisations and the wider international community to focus attention on fulfilling earlier promises to combat global poverty. This international framework for development prioritises: the eradication of extreme poverty and hunger; achieving universal primary education; promoting gender equality and empowering women; reducing child mortality; improving maternal health; combating HIV/AIDS, malaria and other diseases; ensuring environmental sustainability; and developing a global partnership for development. These goals have been mapped onto specific targets (18 in total) against which outcomes of associated development initiatives can be measured and the international community held to account. If the world achieves the MDGs, more than 500 million people will be lifted out of poverty. However, the challenges the goals represent are formidable. Interim reports on the initiative indicate a need to scale-up efforts and accelerate progress.
Only MDG 7, Target 11 explicitly identifies shelter as a priority, identifying the need to secure ‘by 2020 a significant improvement in the lives of at least 100 million slum dwellers’. This raises a question over how Habitat for Humanity’s commitment to tackling poverty housing fits within this broader international framework designed to allievate global poverty. From an analysis of HFH case studies, this report argues that the processes by which Habitat for Humanity tackles poverty housing directly engages with the agenda set by the MDGs. This should not be regarded as a beneficial by-product of the delivery of decent, affordable shelter, but rather understood in terms of the ways in which Habitat for Humanity has translated its mission and values into a participatory model that empowers individuals and communities to address the interdependencies between inadequate shelter and other sources of human insecurity. What housing can deliver is as important as what housing itself is.

Examples of the ways in which Habitat for Humanity projects engage with the MDG framework include the incorporation of sustainable livelihoods strategies, up-grading of basic infrastructure and promotion of models of good governance. This includes housing projects that have also offered training to young people in skills used in the construction industry, microfinanced loans for women to start up their own home-based businesses, and the provision of food gardens. These play an important role in lifting families out of poverty and ensuring the sustainability of HFH projects. Studies of the impact of improved shelter and security of livelihood upon family life and the welfare of children evidence higher rates of participation in education, more time dedicated to study and greater individual achievement. Habitat for Humanity projects also typically incorporate measures to up-grade the provision of basic sanitation facilities and supplies of safe, potable drinking water. These measures not only directly help reduce mortality rates (e.g. diarrheal diseases account for around 2 million deaths annually in children under 5), but also, when delivered through HFH project-related ‘community funds’, empower the poor to mobilise community resources, develop local leadership capacities and even secure de facto security of tenure from government authorities.

In the process of translating its mission and values into practical measures, HFH has developed a range of innovative practices that deliver much more than housing alone. The organisation’s participatory model enables both direct beneficiaries and the wider community to tackle the insecurities they face, unlocking latent skills and enterprise, building sustainable livelihood capabilities. HFH plays an important role as a catalyst for change, delivering through the vehicle of housing the means to address the primary causes of poverty itself. Its contribution to wider development priorities deserves better recognition. In calibrating the success of HFH projects in terms of units completed or renovated alone, the significance of the process by which HFH realises these outcomes is often not sufficiently acknowledged, both within the organisation and externally. As the case studies developed in the report illustrate, the methodologies Habitat for Humanity employs to address the issue of poverty housing within the developing world, place the organisation at the centre of a global strategic agenda to address the root causes of poverty through community empowerment and the transformation of structures of governance.

Given this, the global network of HFH affiliates constitutes a unique organisational framework to faciliate sharing resources, ideas and practical experience across a diverse range of cultural, political and institutional environments. This said, it is apparent that work needs to be done to better to faciliate the pooling of experience and lessons learnt from across its affiliates. Much is to be gained from learning from less successful projects, sharing innovative practices, identifying strategic partnerships with donors, other NGOs and CBOs, and engaging with the international development community on how housing fits within a broader agenda to alleviate poverty and promote good governance.

Development of selective media for the isolation of yeasts and filamentous fungi from the sputum of adult patients with cystic fibrosis (CF)

Yeasts and filamentous fungi are beginning to emerge as significant microbial pathogens in patients with cystic fibrosis (CF), particularly in relation to allergic-type responses, as seen in patients with allergic bronchopulmonary aspergillosis (ABPA), Aspergillus bronchitis and in invasive fungal disease in lung transplant patients. Four fungal media were compared in this study, including Sabouraud Dextrose Agar (SDA) and Medium B, with and without the addition of selective antibiotics, where antibiotic-supplemented media were designated with (+). These media were compared for their ability to suppress contaminating, mainly Gram-ve pathogens, in CF sputa (Pseudomonas aeruginosa, Burkholderia cepacia complex [BCC] organisms) and to enhance the growth of fungi present in CF sputum. Medium B consisted of glucose (16.7 g/l), agar (20 g/l), yeast extract (30 g/l) and peptone (6.8 g/l) at pH 6.3 and both SDA(+) and Medium B+ were supplemented with cotrimethoxazole, 128 mg/l; chloramphenicol, 50 mg/l; ceftazidime, 32 mg/l; colistin, 24 mg/l). Employment of SDA(+) or Medium B+ allowed an increase in specificity in the detection of yeasts and moulds, by 42.8% and 39.3%, respectively, over SDA when used solely. SDA(+) had a greater ability than Medium B+ to suppress bacterial growth from predominantly Gram-ve co-colonisers. This is a significant benefit when attempting to detect and isolate fungi from the sputum of CF patients, as it largely suppressed any bacterial growth, with the exception of the BCC organisms, thus allowing for an increased opportunity to detect target fungal organisms in sputum and represented a significant improvement over the commercial medium (SDA), which is currently used. Overall, both novel selective media were superior in their ability to suppress bacteria in comparison with the commercially available SDA medium, which is routinely employed in most clinical microbiology diagnostic laboratories presently. Alternatively, Medium B+ had a great ability to grow fungi than SDA(+) and when employed together, the specificity of combined use was 82%, with a sensitivity for yeasts, filamentous fungi, and combined overall fungi of 96.0%, 92.3% and 96.0%, respectively. Overall, when employing one fungal selective medium for the routine detection of yeasts and filamentous fungi in the sputum of CF patients, we would recommend employment of Medium B+. However, we would recommend the combined employment of SDA(+) and Medium B+, in order to synergistically isolate and detect the greatest number of fungi present in CF sputa. (C) 2008 European Cystic Fibrosis Society. Published by Elsevier B.V All rights reserved.

The replacement of a native freshwater amphipod by an invader: roles for environmental degradation and intraguild predation

We assessed the extent to which an invader, Gammarus pulex (Crustacea: Amphipoda), has replaced a native, Gammarus duebeni celticus, over a 13-year period in a European river system and some of the abiotic and biotic factors that could account for this. Between 1988 and 2001, 56% of mixed-species sites had become invader-only sites, whereas no mixed sites had become native only again. The native dominated areas of higher dissolved oxygen and water quality, with the reciprocal true for the invader. Field transplant experiments revealed that native survivorship was lower in areas where it had been replaced than in areas where the invader does not yet occur. In invader-only areas, native survivorship was lower than that of the invader when kept separately and lowest when both species were kept together. We also observed predation of the native by the invader. Laboratory oxygen manipulation experiments revealed that at 30% saturation, the native's survivorship was two thirds that of the invader. We conclude that decreasing water quality favours replacement of the native by the invader.

Differential physico-chemical tolerances and intraguild predation among native and invasive amphipods (Crustacea); a field study

We used field surveys and transplant experiments to elucidate the relative roles of physico-chemical regime and intraguild predation in determining the generally mutually exclusive distributions of native and invader freshwater amphipod species. Field surveys showed that the native Gammarus duebeni celticus dominates the shoreline of Lough Neagh, N. Ireland, with some co-occurrence with the N. American invader G. tigrinus. However, the latter species dominates the deeper areas of the mid-Lough. Transplant experiments showed no difference in survival of the native and invader in single species 'bioassay tubes' placed along the shoreline. However, there was significantly higher survival of the invader compared with the native in single species tubes placed in the mid-Lough. In mixed species tubes on the shoreline, the native killed and ate the invader, with no reciprocal interaction, leading to significant reductions of the invader. However, the invader had significantly higher survival than the native in mixed species tubes in the mid-Lough, with no evidence. of predation between the two species. These results indicate that, whereas differential intraguild predation may determine domination of the shoreline by the native, differential physico-chemical tolerances may be major determinants of the domination of the mid-Lough by the invader. This study emphasises the need to consider the habitat template in conjunction with biotic interactions before attempting to draw conclusions about mechanisms determining relative distribution patterns of native and invasive species.

Pim2 cooperates with PML-RAR alpha to induce acute myeloid leukemia in a bone marrow transplantation model

Although the potential role of Pim2 as a cooperative oncogene has been well described in lymphoma, its role in leukemia has remained largely unexplored. Here we show that high expression of Pim2 is observed in patients with acute promyelocytic leukemia (APL). To further characterize the cooperative role of Pim2 with promyelocytic leukemia/retinoic acid receptor alpha (PML/RAR alpha), we used a well-established PML-RAR alpha (PR alpha) mouse model. Pim2 coexpression in PR alpha-positive hematopoietic progenitor cells (HPCs) induces leukemia in recipient mice after a short latency. Pim2-PR alpha cells were able to repopulate mice in serial transplantations and to induce disease in all recipients. Neither Pim2 nor PR alpha alone was sufficient to induce leukemia upon transplantation in this model. The disease induced by Pim2 overexpression in PR alpha cells contained a slightly higher fraction of immature myeloid cells, compared with the previously described APL disease induced by PR alpha. However, it also clearly resembled an APL-like phenotype and showed signs of differentiation upon all-trans retinoic acid (ATRA) treatment in vitro. These results support the hypothesis that Pim2, which is also a known target of Flt3-ITD (another gene that cooperates with PML-RAR alpha), cooperates with PR alpha to induce APL-like disease. (Blood. 2010; 115(22): 4507-4516)

Methadone as Social Control: Institutionalized Stigma and the Prospect of Recovery

Methadone maintenance treatment (MMT) is an intervention used to treat opioid (heroin) dependence. Several investigators have found that MMT is effective in reducing heroin use and other behaviors; however, a disproportionate number of MMT clients leave treatment prematurely. Moreover, MMT outcome variables are often limited in terms of their measurement. Utilizing an integrated theoretical framework of social control and stigma, we focused on the experiences of methadone maintenance from the perspective of clients. We pooled interview data from four qualitative studies in two jurisdictions and found linkages between social control and institutional stigma that serve to reinforce "addict" identities, expose undeserving customers to the public gaze, and encourage clients to be passive recipients of treatment. We discuss the implications for recovery and suggest recommendations for change.

Charged experience's of natural environments

Natural environments often generate experiences that combine great emotional and moral power- "charged" experiences. Their characteristics are explored through writings that capture them convincingly. They appear to have a perceptual character. Perception of the scene is invested with a sense of something beyond it, and much bigger. It may be God, or immensity in time or space, or the essence of a nation. This encounter is often connected with moral authority. A recurring theme is the sense that environment and the things in it-including the observer-are a self-similar pattern. People are not passive recipients of these experiences. They seek them out. Evoking, the environment in words can often evoke the charged experience too-at least in part. The material suggests tasks for psychologists-most simply, finding systematic ways to describe these experiences. That may help other environmental disciplines, which face difficulty characterising the dimension of response. Theoretically, the material raises questions about the representations generated by perceptual processes. The observation that powerful moral imperatives seem to be given in the act of perceiving is also suggestive for the psychology of morality. Culture certainly plays a part in charged responses, but landscapes have the power to be invested with an emotional and moral charge where other stimuli may not.

Donor identification and consent for deceased organ donation: summary of NICE guidance.

Organ donation plays a major role in the management of patients with single organ failure of the kidneys, liver, pancreas, heart, or lung, or with combined organ failure of heart and lung (such as in cystic fibrosis) or of kidney and pancreas (such as in diabetes). A shortage of transplant organs has resulted in long waits for transplantation. Currently about 500 people in the United Kingdom die each year because of a shortage of donated organs,1 and at 31 March 2011 almost 7000 patients were waiting for a kidney transplant1 and would be having costly dialysis with serious morbidity and impact on quality of life. This shortage of organs is partly the result of relatively low numbers of road traffic deaths (lower than in many countries) but is also the result of inefficiencies in the donor identification and consent processes. This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on improving donor identification and consent rates for deceased organ donation.2