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This thesis investigates the potential of GeoWeb 2.0, the interactive geospatial capabilities of the internet, to facilitate broad-based community participation in environmental information sharing and environmental management. Environmental sustainability is a challenge confronting the whole of humanity. Creation and sharing of information is foundational in efforts to address environmental sustainability. GeoWeb 2.0 and related practices, such as volunteering geographic information and Neogeography, have been heralded as a revolution in information sharing, with potentially transformational and disruptive consequences. GeoWeb 2.0 is already being harnessed for information sharing to support environmental sustainability efforts. However, this capacity brings both opportunities and risks hence applications of GeoWeb 2.0 deserve close examination. Action Research was used to engage with research participants, as individuals and in small groups in the researcher's local community and within institutions operating at larger scales, in both online and offline contexts. Participant Action Research was first used to engage with individuals on and offline to share information about the state of their environment. Action Research and Participant Observation were used to engage with other existing initiatives and organisations to investigate their use of GeoWeb 2.0. I participated directly in the study, including an auto-ethnographical study of my own practice. Other evidence was gathered from the literature, web resources and applications. A broad range of criteria for quality were established and critical reflexivity employed throughout the research. A narrative writing style was used to make explicit the recursive development, and the role of time and place, in construction of the research. Issues with traditional environmental information sharing that can be addressed through GeoWeb 2.0 were identified through a discussion of environmental sustainability, its information requirements, issues with State of the Environment reporting, and GeoWeb 2.0 capabilities. GeoWeb 2.0 can lower barriers to community sharing of environmental information, and has potential for addressing the issues identified for environmental information sharing. This research indicated, however, that the potential may be difficult to achieve as many barriers to participation exist and are emerging, and that broad-based sharing was not identified, demonstrated or considered likely through GeoWeb 2.0 alone. While it is possible that GeoWeb 2.0 can contribute to the representation of pluralistic conceptualisations of environmental sustainability that are nuanced to particular contexts, a definitive evaluation is confounded by the potential for the emergence of unintended consequences from complex interactions at broader scales. This research contributes to a more complex and nuanced understanding of GeoWeb 2.0's role in supporting community sharing of information that promotes environmental sustainability. It critiques dominant views espousing simplistic and deterministic views of the outcomes for GeoWeb 2.0, in particular that openness is a major characteristic. In some instances, openness is an objective and features that contribute to this can be identified, but it is a concept that is conditional on the local context. Other quality criteria should be used to evaluate any approach that considers using GeoWeb 2.0 including inclusive, representative, accessible, transparent, free, equitable, balanced (ing), collaborative, adaptable and reusable. An insight arising from the research is that Action Research methods can contribute to the development of GeoWeb 2.0 applications that share environmental information in support of sustainability. This is because its recursive nature is responsive to the complexity of the evolving context, and critical reflexivity allows for continual assessment of ethical concerns arising from emergent outcomes. Practically, the research reviews and demonstrates how GeoWeb 2.0 can be used by individuals and collectives to discover and share relevant information, and how this can affect real changes in environmental conditions.

The importance of interactions, activities and environments for improving quality of life for people living with dementia and their carers.

The importance of social programmes that activate\ud the built environment, responding to the diverse\ud (social, medical or cultural) needs and aspirations of\ud older people.

The publication last month (August 2021) of the World Health Organization’s toolkit for creating a dementia-friendly society marks the latest step in the coordination of a worldwide effort to tackle dementia as a global health challenge. But what does dementia-friendliness mean in practice, and whose purposes and interests do these initiatives ultimately serve?

This case study outlines the development and implementation of a mobile-focus group technique. Ostensibly, this is a blending of various aspects of conventional focus group and mobile interview methods. The case study was developed as one of a suite of methods used to evaluate a series of national-level interventions to promote the active inclusion and participation of young people in the quasi-formal development, and day-to-day activities in, a variety of deprived, predominantly urban, neighbourhoods in the UK. The method involved a group of young people leading researchers (and evaluators) on a guided tour of their neighbourhood. From the outset, the aim is to place participants in charge of where to go, and where not to go, and what to reveal and (perhaps) what to keep hidden. So, the young people adopt the role of local tour guides or experts, ‘showing’ their neighbourhood to an ‘interested stranger’. The case study outlines the rationale for developing the approach, presents a step-by-step account of how the approach was deployed, and details of practical considerations and challenges researchers may face when using the approach. The case study concludes by considering how the mobile and interactional dimensions of the method might recreate authentic ways in which local places are produced and experienced.

Walking interviews have been used with growing frequency to understand the relationships between people, spaces and social worlds, but they typically rely on a single researcher-participant relationship. In Andrew Clarks’ ‘Walking Together: Understanding Young People’s Experiences of Living in Neighbourhoods in Transition’, we amble in groups through neighbourhoods and territories, taking in the parks and shelters that offer places to gather. Introducing a mobile focus group method as a way of understanding young people’s individual and collective experiences of life in deprived urban neighbourhoods across England, the chapter outlines the challenges and opportunities afforded by the approach and reflects on the implications for knowledge arising from this collective and interactive method.

Background: The treatment of chronic pain is still unsatisfactory. Despite the availability of different drugs, most patients with chronic pain do not receive satisfactory pain relief or report side effects. Converging evidence implicates involvement of the immune system in the pathogenesis of different types of nociceptive and neuropathic chronic pain. Design: At a workshop in Liverpool, UK (October 2012), experts presented evidence suggesting immunological involvement in chronic pain and recent data supporting the concept that the established immune-modulating drug, polyvalent immunoglobulin G (IgG), either given intravenously (IVIg) or subcutaneously (SCIg), may reduce pain in some peripheral neuropathies and a range of other pain disorders. Workshop's attendees discussed the practicalities of using IVIg and SCIg in these disorders, including indications, cost-effectiveness, and side effects. Results: IgG may reduce pain in a range of nociceptive and neuropathic chronic pain conditions, including diabetes mellitus, Sjögren's syndrome, fibromyalgia, complex regional pain syndrome, post-polio syndrome, and pain secondary to pathological autoantibodies. Conclusions: IgG is a promising treatment in several chronic pain conditions. IgG is a relatively safe therapeutic strategy, with uncommon and mild side effects but high costs. Randomized, controlled trials and predictive tests are needed to better support the use of IgG for refractory chronic pain. © 2014 Wiley Periodicals, Inc.

Object: Glioblastomas are difficult tumors to eradicate because of resistance to apoptosis and other mechanisms of programmed cell death such as autophagy. We hypothesized that DNA damage, regardless of etiology, would cause autophagy. To test our hypothesis, we examined the ability of two DNA damaging agents, 1, 3-Bis (2-chloroethyl)-1-nitrosourea (BCNU) and cisplatin, to induce autophagy. Materials and methods: DNA damage was assessed by western blot for γ-H2AX and immunofluorescence for phospho-53BP1. Autophagy was measured by microtubule-associated protein 1 light chain (LC3) and beclin 1 western blots, acridine orange staining, response to the 3-MA inhibitor, and autophagosome detection using electron microscopy. To study apoptosis, we examined levels of BAX and BAK, TUNEL staining, inhibition with ZVAD.fmk and caspase 3/7 activation. Results: The levels of the DNA damage indicators γ-H2AX and 53BP1 increased with both BCNU and cisplatin. While LC3-II autophagy proteins were highly expressed in BCNU samples, LC3-II levels were below the limits of detection in cells treated with cisplatin. Caspase 3/7 activation only slightly increased with BCNU, but markedly increased with cisplatin. Surprisingly, BAX and BAK levels did not change in response to either chemotherapeutic compound. Significant TUNEL staining was evident in cisplatin, but not BCNU-treated cells, and the pancaspase inhibitor, ZVAD.fmk, did not diminish cell death after BCNU treatment. Conclusion: Although both drugs caused DNA damage, we concluded not all DNA damage results in a specific type of cell death, as BCNU-related cell death in glioblastomas occurs through autophagy and cisplatin predominantly induces apoptosis. The specific molecular mechanisms underlying the activation of autophagy remain obscure.

This paper looks at medium-scale renewable energy systems suitable for community-level developments, exploring the impact of the planning system on the scope for deployment and identifying ways of keeping schemes within limits that are likely to be acceptable. It pays particular attention to environmentally sensitive locations such as areas of outstanding natural beauty. The findings, which are generally applicable in a UK environment, are exemplified and demonstrated by means of a case study based on an area of outstanding natural beauty in north east England in which there is local community interest in sustainability matters generally. Systems considered include air source heat pumps, biomass heating, wind energy, solar photovoltaic and anaerobic digestion.

A variety of transgenic animal species are beingused to produce recombinant proteins. The generalapproach is to target the expression of the desiredprotein to the mammary gland using regulatory elements derived from a milk protein gene and thencollect and purify the product from milk. Promotersequences from a number of different milk protein geneshave been used to target expression to the mammarygland, although significant problems remain withregard to achieving transgene expression levelsconsistent with commercial exploitation. The mammarygland appears to be capable of carrying out the complexposttranslational modifications, such as glycosylation andγ-carboxylation required for the biologicalactivity and stability of specific proteins. Effectivepurification protocols have been established andproducts produced by this route have now enteredclinical trials.

Objective: Craniopharyngiomas are rare tumors with bimodal incidence in the pediatric and adult age groups. Treatment strategies range from aggressive resection to planned limited resection combined with adjuvant therapies. Currently there is no consensus for standard of care for pediatric craniopharyngioma. Materials and methods: We performed a systematic review of the published literature on pediatric craniopharyngioma. Patients were grouped based on extent of resection into gross total resection (GTR), subtotal resection (STR), and biopsy procedures. These groups were compared with respect to tumor control. Chi square was used to compare rates of recurrence. Kaplan-Meier was used to generate progression-free survival (PFS) estimates. Cox proportional hazard modeling was used to evaluate risk of progression. Each extent of resection group was also subdivided based on adjuvant therapy and compared. Results: A total of 109 studies described extent of resection resulting in a cohort of 531 patients. Recurrence data were available for 377 patients. There was no difference in 1- or 5-year PFS between the groups who underwent GTR and STR combined with radiation (XRT; log-rank; p = 0.76; 1-year PFS 89 vs 84 %25; 5-year PFS 77 vs 73 %25, respectively). One-year PFS was 84 %25 for STR+XRT compared to 76 %25 for STR alone while 5-year PFS was 73 %25 for STR+XRT compared to 43 %25 for STR alone (log-rank; p = 0.003). Conclusion: Although there are limitations of a systematic review of retrospective data, our results suggest that STR+XRT of pediatric craniopharyngioma is associated with similar rates of tumor control as GTR. © 2012 Springer-Verlag.

SUMMARYThe minimal hormonal requirements for inducing the ovine β-lactoglobulin gene have been investigated using mammary gland explants from ewes in the first half of pregnancy. Quantification of β-lactoglobulin mRNA showed that a combination of insulin, Cortisol and prolactin was required to stimulate the expression of the gene and that this response could not be enhanced by the addition of oestrogen and thyroid hormone to the culture medium. Explants cultured in the presence of insulin, Cortisol and prolactin also demonstrated the capacity to synthesize the protein. Progesterone did not inhibit the induction of the gene, which is consistent with the increase in β-lactoglobulin mRNA observed in vivo in the mammary gland during the final 2 months of pregnancy when the circulating level of progesterone is elevated.

Background: The leukocyte common antigen related receptor (LAR) protein has been shown to modulate the signal transduction of a number of different growth factors, including insulin and insulin-like growth factor 1. Splice variants exhibit differing roles and are expressed according to tissue type and developmental stage.\ud \ud Results: Using 5'RACE, we identified a 5'UTR within intron 11 of the rat LAR gene. We demonstrated that this gives rise to a novel isoform of the LAR transcript encoded from the identified region within intron 11. By priming across the site from exon 11 to exon 15 we show that the novel 5'UTR is not represented in the full-length transcript and thus, it produces a truncated form of the LAR mRNA. We examined the tissue distribution of this novel isoform and\ud found it to be exclusively expressed in liver. We additionally identified a liver specific 150 kDa band\ud with western blotting which we propose may represent the protein product of the novel transcript. Luciferase assays showed the region immediately upstream of the 5'UTR to possesses considerable promoter activity and that this may be conferred by the presence of a number of putative binding\ud sites for liver enriched transcription factors.\ud \ud Conclusion: In summary, we describe a novel, liver specific, truncated isoform of the LAR transcript transcribed under the control of an intronic promoter, potentially representing a previously unidentified modulator of hepatic insulin signalling.

Objective: The polymorphic deletion of exon 3 of the GH receptor (d3-GHR) has recently been linked to the magnitude of growth response to recombinant human GH (rhGH) therapy in short children with or without GH deficiency. We investigated this association in a large multinational cohort from the Network of European Studies of Genes in Growth (NESTEGG), comprising short children born small for gestational age (SGA).\ud \ud Design: The study included short prepubertal SGA children treated with rhGH for 1 or 2 years.\ud \ud Population: Two hundred and forty white Caucasian SGA children (138 male, 102 female) aged 6·6 ± 2·3 years with a height at –3·0 ± 0·7 SDS at start of rhGH treatment; 193 ethnically matched controls.\ud \ud Methods: The GHR polymorphism (fl/fl, fl/d3 or d3/d3) was genotyped by polymerase chain reaction (PCR) multiplex assay. Growth velocity (G/V) in cm/year and changes in GV during the first and second year of rhGH treatment were evaluated.\ud \ud Results: The change in GV was significantly greater in SGA children carrying one or two copies of the d3-GHR allele (P = 0·038 for the first year and P = 0·041 for the second year of GH treatment), but the change in height was not significantly different. Birthweight was significantly lower in SGA children with the d3/d3 genotype than in SGA children with the fl/fl genotype (P = 0·034) and in those with the fl/d3 genotype (P = 0·016).\ud \ud Conclusion: Our data, based on a large cohort, showed that the exon 3 GHR polymorphism is associated with responsiveness to rhGH treatment in SGA children with short stature.

OBJECTIVE: To provide clinicians with guidelines for the use of cannabinoid compounds in the treatment of chronic pain.METHODS: Publications indexed from 1990 to 2005 in the National Library of Medicine Index Medicus were searched through PubMed. A consensus concerning these guidelines was achieved by the authors through review and discussion.RESULTS: There are few clinical trials, case reports or case series concerning the use of cannabinoid compounds in the treatment of chronic pain. There are no randomized clinical trials examining the use of herbal cannabis in the treatment of chronic pain.CONCLUSIONS: A practical approach to the treatment of chronic pain with cannabinoid compounds is presented. Specific suggestions about the off-label dosing of nabilone (Cesamet, Valeant Canada limitée/Limited) and dronabinol (Marinol, Solvay Pharma Inc, Canada) in the treatment of chronic pain are provided.