Religion and spirituality in the spaces of the primary school : social and political explorations

This thesis explores the issue of religion and spirituality in the spaces of the primary school through the employment of a mixed-method, qualitative approach. It includes a comparison between two case study schools - a Community primary and a Roman Catholic primary - both in multi-faith areas of an urban location in the North of England. By using a spatial and child-centreC! focus, the research investigates the social and political role and significance of religion, and spirituality for children, parents and teaching staff in the study schools .. This is achieved through attention to four different spaces and their interconnections with institutional space. The first is the nation, where the thesis explores how the two different schools advocated distinct types of religious citizenship and approaches to accommodating religious minorities on an everyday basis. The second space is the community, and the various ways in which the schools promoted social cohesion through the encouragement of positive encounters between children from different religious backgrounds, and the development of a sense of embodied togetherness. The third spatial focus concerns the extent to which religion inhabits public or private space in school ethos. The caring nature of school ethos in the two different contexts is also explored and the consequences for child participation in school life. The fourth and final space is that of the body within informal school spaces, where the focus is on the role of children's embodied religious and spiritual practices for re-envisaging understandings of school ethos and practice. The thesis makes original contributions to theoretical, methodological and empirical knowledge, including the significance of emot,ipns .and spirituality, understandings of children's agency, the use of child-centred methods as part of a mixed-method approach, and the role of religion in secular space, education and wider society

Management and control of tuberculosis control in socially complex groups: a research programme including three RCTs

Background: Socially complex groups, including people experiencing homelessness, prisoners and drug users, have very high levels of tuberculosis, often complicated by late diagnosis and difficulty in adhering to treatment. / Objective: To assess a series of interventions to improve tuberculosis control in socially complex groups. / Design: A series of observational surveys, evaluations and trials of interventions. / Setting: The pan-London Find&Treat service, which supports tuberculosis screening and case management in socially complex groups across London. / Participants: Socially complex groups with tuberculosis or at risk of tuberculosis, including people experiencing homelessness, prisoners, drug users and those at high risk of poor adherence to tuberculosis treatment. Interventions and main outcome measures We screened 491 people in homeless hostels and 511 people in prison for latent tuberculosis infection, human immunodeficiency virus, hepatitis B and hepatitis C. We evaluated an NHS-led prison radiographic screening programme. We conducted a cluster randomised controlled trial (2348 eligible people experiencing homelessness in 46 hostels) of the effectiveness of peer educators (22 hostels) compared with NHS staff (24 hostels) at encouraging the uptake of mobile radiographic screening. We initiated a trial of the use of point-of-care polymerase chain reaction diagnostics to rapidly confirm tuberculosis alongside mobile radiographic screening. We undertook a randomised controlled trial to improve treatment adherence, comparing face-to-face, directly observed treatment with video-observed treatment using a smartphone application. The primary outcome was completion of ≥ 80% of scheduled treatment observations over the first 2 months following enrolment. We assessed the cost-effectiveness of latent tuberculosis screening alongside radiographic screening of people experiencing homelessness. The costs of video-observed treatment and directly observed treatment were compared. / Results: In the homeless hostels, 16.5% of people experiencing homelessness had latent tuberculosis infection, 1.4% had current hepatitis B infection, 10.4% had hepatitis C infection and 1.0% had human immunodeficiency virus infection. When a quality-adjusted life-year is valued at £30,000, the latent tuberculosis screening of people experiencing homelessness was cost-effective provided treatment uptake was ≥ 25% (for a £20,000 quality-adjusted life-year threshold, treatment uptake would need to be > 50%). In prison, 12.6% of prisoners had latent tuberculosis infection, 1.9% had current hepatitis B infection, 4.2% had hepatitis C infection and 0.0% had human immunodeficiency virus infection. In both settings, levels of latent tuberculosis infection and blood-borne viruses were higher among injecting drug users. A total of 1484 prisoners were screened using chest radiography over a total of 112 screening days (new prisoner screening coverage was 43%). Twenty-nine radiographs were reported as potentially indicating tuberculosis. One prisoner began, and completed, antituberculosis treatment in prison. In the cluster randomised controlled trial of peer educators to increase screening uptake, the median uptake was 45% in the control arm and 40% in the intervention arm (adjusted risk ratio 0.98, 95% confidence interval 0.80 to 1.20). A rapid diagnostic service was established on the mobile radiographic unit but the trial of rapid diagnostics was abandoned because of recruitment and follow-up difficulties. We randomly assigned 112 patients to video-observed treatment and 114 patients to directly observed treatment. Fifty-eight per cent of those recruited had a history of homelessness, addiction, imprisonment or severe mental health problems. Seventy-eight (70%) of 112 patients on video-observed treatment achieved the primary outcome, compared with 35 (31%) of 114 patients on directly observed treatment (adjusted odds ratio 5.48, 95% confidence interval 3.10 to 9.68; p < 0.0001). Video-observed treatment was superior to directly observed treatment in all demographic and social risk factor subgroups. The cost for 6 months of treatment observation was £1645 for daily video-observed treatment, £3420 for directly observed treatment three times per week and £5700 for directly observed treatment five times per week. / Limitations: Recruitment was lower than anticipated for most of the studies. The peer advocate study may have been contaminated by the fact that the service was already using peer educators to support its work. / Conclusions: There are very high levels of latent tuberculosis infection among prisoners, people experiencing homelessness and drug users. Screening for latent infection in people experiencing homelessness alongside mobile radiographic screening would be cost-effective, providing the uptake of treatment was 25–50%. Despite ring-fenced funding, the NHS was unable to establish static radiographic screening programmes. Although we found no evidence that peer educators were more effective than health-care workers in encouraging the uptake of mobile radiographic screening, there may be wider benefits of including peer educators as part of the Find&Treat team. Utilising polymerase chain reaction-based rapid diagnostic testing on a mobile radiographic unit is feasible. Smartphone-enabled video-observed treatment is more effective and cheaper than directly observed treatment for ensuring that treatment is observed. / Future work: Trials of video-observed treatment in high-incidence settings are needed. / Trial registration: Current Controlled Trials ISRCTN17270334 and ISRCTN26184967. / Funding: This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 8, No. 9. See the NIHR Journals Library website for further project information

Identification of β-Secretase (BACE1) Substrates Using Quantitative Proteomics

β-site APP cleaving enzyme 1 (BACE1) is a transmembrane aspartyl protease with a lumenal active site that sheds the ectodomains of membrane proteins through juxtamembrane proteolysis. BACE1 has been studied principally for its role in Alzheimer's disease as the β-secretase responsible for generating the amyloid-β protein. Emerging evidence from mouse models has identified the importance of BACE1 in myelination and cognitive performance. However, the substrates that BACE1 processes to regulate these functions are unknown, and to date only a few β-secretase substrates have been identified through candidate-based studies. Using an unbiased approach to substrate identification, we performed quantitative proteomic analysis of two human epithelial cell lines stably expressing BACE1 and identified 68 putative β-secretase substrates, a number of which we validated in a cell culture system. The vast majority were of type I transmembrane topology, although one was type II and three were GPI-linked proteins. Intriguingly, a preponderance of these proteins are involved in contact-dependent intercellular communication or serve as receptors and have recognized roles in the nervous system and other organs. No consistent sequence motif predicting BACE1 cleavage was identified in substrates versus non-substrates. These findings expand our understanding of the proteins and cellular processes that BACE1 may regulate, and suggest possible mechanisms of toxicity arising from chronic BACE1 inhibition

Centile charts for birthweight for gestational age for Scottish singleton births

<p>Abstract</p> <p>Background</p> <p>Centile charts of birthweight for gestational age are used to identify low birthweight babies. The charts currently used in Scotland are based on data from the 1970s and require updating given changes in birthweight and in the measurement of gestational age since then.</p> <p>Methods</p> <p>Routinely collected data of 100,133 singleton births occurring in Scotland from 1998–2003 were used to construct new centile charts using the LMS method.</p> <p>Results</p> <p>Centile charts for birthweight for sex and parity groupings were constructed for singleton birth and compared to existing charts used in Scottish hospitals.</p> <p>Conclusion</p> <p>Mean birthweight has been shown to have increased over recent decades. The differences shown between the new and currently used centiles confirm the need for more up-to-date centiles for birthweight for gestational age.</p

Suppression of Plant Resistance Gene-Based Immunity by a Fungal Effector

The innate immune system of plants consists of two layers. The first layer, called basal resistance, governs recognition of conserved microbial molecules and fends off most attempted invasions. The second layer is based on Resistance (R) genes that mediate recognition of effectors, proteins secreted by pathogens to suppress or evade basal resistance. Here, we show that a plant-pathogenic fungus secretes an effector that can both trigger and suppress R gene-based immunity. This effector, Avr1, is secreted by the xylem-invading fungus Fusarium oxysporum f.sp. lycopersici (Fol) and triggers disease resistance when the host plant, tomato, carries a matching R gene (I or I-1). At the same time, Avr1 suppresses the protective effect of two other R genes, I-2 and I-3. Based on these observations, we tentatively reconstruct the evolutionary arms race that has taken place between tomato R genes and effectors of Fol. This molecular analysis has revealed a hitherto unpredicted strategy for durable disease control based on resistance gene combinations

Evidence and perceptions of rainfall change in Malawi: Do maize cultivar choices enhance climate change adaptation in sub-Saharan Africa?

Getting farmers to adopt new cultivars with greater tolerance for coping with climatic extremes and variability is considered as one way of adapting agricultural production to climate change. However, for successful adaptation to occur, an accurate recognition and understanding of the climate signal by key stakeholders (farmers, seed suppliers and agricultural extension services) is an essential precursor. This paper presents evidence based on fieldwork with smallholder maize producers and national seed network stakeholders in Malawi from 2010 to 2011, assessing understandings of rainfall changes and decision-making about maize cultivar choices. Our findings show that preferences for short-season maize cultivars are increasing based on perceptions that season lengths are growing shorter due to climate change and the assumption that growing shorter-season crops represents a good strategy for adapting to drought. However, meteorological records for the two study areas present no evidence for shortening seasons (or any significant change to rainfall characteristics), suggesting that short-season cultivars may not be the most suitable adaptation option for these areas. This demonstrates the dangers of oversimplified climate information in guiding changes in farmer decision-making about cultivar choice

Peripheral Delivery of a CNS Targeted, Metalo-Protease Reduces Aβ Toxicity in a Mouse Model of Alzheimer's Disease

Alzheimer's disease (AD), an incurable, progressive neurodegenerative disorder, is the most common form of dementia. Therapeutic options have been elusive due to the inability to deliver proteins across the blood-brain barrier (BBB). In order to improve the therapeutic potential for AD, we utilized a promising new approach for delivery of proteins across the BBB. We generated a lentivirus vector expressing the amyloid β-degrading enzyme, neprilysin, fused to the ApoB transport domain and delivered this by intra-peritoneal injection to amyloid protein precursor (APP) transgenic model of AD. Treated mice had reduced levels of Aβ, reduced plaques and increased synaptic density in the CNS. Furthermore, mice treated with the neprilysin targeting the CNS had a reversal of memory deficits. Thus, the addition of the ApoB transport domain to the secreted neprilysin generated a non-invasive therapeutic approach that may be a potential treatment in patients with AD

Genome-wide SNPs and re-sequencing of growth habit and inflorescence genes in barley: implications for association mapping in germplasm arrays varying in size and structure

<p>Abstract</p> <p>Background</p> <p>Considerations in applying association mapping (AM) to plant breeding are population structure and size: not accounting for structure and/or using small populations can lead to elevated false-positive rates. The principal determinants of population structure in cultivated barley are growth habit and inflorescence type. Both are under complex genetic control: growth habit is controlled by the epistatic interactions of several genes. For inflorescence type, multiple loss-of-function alleles in one gene lead to the same phenotype. We used these two traits as models for assessing the effectiveness of AM. This research was initiated using the CAP Core germplasm array (n = 102) assembled at the start of the Barley Coordinated Agricultural Project (CAP). This array was genotyped with 4,608 SNPs and we re-sequenced genes involved in morphology, growth and development. Larger arrays of breeding germplasm were subsequently genotyped and phenotyped under the auspices of the CAP project. This provided sets of 247 accessions phenotyped for growth habit and 2,473 accessions phenotyped for inflorescence type. Each of the larger populations was genotyped with 3,072 SNPs derived from the original set of 4,608.</p> <p>Results</p> <p>Significant associations with SNPs located in the vicinity of the loci involved in growth habit and inflorescence type were found in the CAP Core. Differentiation of true and spurious associations was not possible without <it>a priori </it>knowledge of the candidate genes, based on re-sequencing. The re-sequencing data were used to define allele types of the determinant genes based on functional polymorphisms. In a second round of association mapping, these synthetic markers based on allele types gave the most significant associations. When the synthetic markers were used as anchor points for analysis of interactions, we detected other known-function genes and candidate loci involved in the control of growth habit and inflorescence type. We then conducted association analyses - with SNP data only - in the larger germplasm arrays. For both vernalization sensitivity and inflorescence type, the most significant associations in the larger data sets were found with SNPs coincident with the synthetic markers used in the CAP Core and with SNPs detected via interaction analysis in the CAP Core.</p> <p>Conclusions</p> <p>Small and highly structured collections of germplasm, such as the CAP Core, are cost-effectively phenotyped and genotyped with high-throughput markers. They are also useful for characterizing allelic diversity at loci in germplasm of interest. Our results suggest that discovery-oriented exercises in AM in such small arrays may generate a large number of false-positives. However, if haplotypes in candidate genes are available, they may be used as anchors in an analysis of interactions to identify other candidate regions harboring genes determining target traits. Using larger germplasm arrays, genome regions where the principal genes determining vernalization sensitivity and row type are located were identified.</p

The USDA Barley Core Collection:Genetic Diversity, Population Structure, and Potential for Genome-Wide Association Studies

New sources of genetic diversity must be incorporated into plant breeding programs if they are to continue increasing grain yield and quality, and tolerance to abiotic and biotic stresses. Germplasm collections provide a source of genetic and phenotypic diversity, but characterization of these resources is required to increase their utility for breeding programs. We used a barley SNP iSelect platform with 7,842 SNPs to genotype 2,417 barley accessions sampled from the USDA National Small Grains Collection of 33,176 accessions. Most of the accessions in this core collection are categorized as landraces or cultivars/breeding lines and were obtained from more than 100 countries. Both STRUCTURE and principal component analysis identified five major subpopulations within the core collection, mainly differentiated by geographical origin and spike row number (an inflorescence architecture trait). Different patterns of linkage disequilibrium (LD) were found across the barley genome and many regions of high LD contained traits involved in domestication and breeding selection. The genotype data were used to define 'mini-core' sets of accessions capturing the majority of the allelic diversity present in the core collection. These 'mini-core' sets can be used for evaluating traits that are difficult or expensive to score. Genome-wide association studies (GWAS) of 'hull cover', 'spike row number', and 'heading date' demonstrate the utility of the core collection for locating genetic factors determining important phenotypes. The GWAS results were referenced to a new barley consensus map containing 5,665 SNPs. Our results demonstrate that GWAS and high-density SNP genotyping are effective tools for plant breeders interested in accessing genetic diversity in large germplasm collections