Still searching for graves: an analytical strategy for interpreting geophysical data used in the search for “unmarked” graves

Searching for and mapping the physical extent of unmarked graves using geophysical techniques has proven difficult in many cases. The success of individual geophysical techniques for detecting graves depends on a site-by-site basis. Significantly, detection of graves often results from measured contrasts that are linked to the background soils rather than the type of archaeological feature associated with the grave. It is evident that investigation of buried remains should be considered within a 3D space as the variation in burial environment can be extremely varied through the grave. Within this paper, we demonstrate the need for a multi-method survey strategy to investigate unmarked graves, as applied at a “planned” but unmarked pauper’s cemetery. The outcome from this case study provides new insights into the strategy that is required at such sites. Perhaps the most significant conclusion is that unmarked graves are best understood in terms of characterization rather than identification. In this paper, we argue for a methodological approach that, while following the current trends to use multiple techniques, is fundamentally dependent on a structured approach to the analysis of the data. The ramifications of this case study illustrate the necessity of an integrated strategy to provide a more holistic understanding of unmarked graves that may help aid in management of these unseen but important aspects of our heritage. It is concluded that the search for graves is still a current debate and one that will be solved by methodological rather than technique-based arguments.

Causality in Europeanization Research: A Discursive Institutional Analytical Strategy

Discourse analysis as a methodology is perhaps not readily associated with substantive causality claims. At the same time the study of discourses is very much the study of conceptions of causal relations among a set, or sets, of agents. Within Europeanization research we have seen endeavours to develop discursive institutional analytical frameworks and something that comes close to the formulation of hypothesis on the effects of European Union (EU) policies and institutions on domestic change. Even if these efforts so far do not necessarily amount to substantive theories or claims of causality, it suggests that discourse analysis and the study of causality are by no means opposites. The study of Europeanization discourses may even be seen as an essential step in the move towards claims of causality in Europeanization research. This paper deals with the question of how we may move from the study of discursive causalities towards more substantive claims of causality between EU policy and institutional initiatives and domestic change.

Modelling in the evaluation of a manufacturing strategy

This thesis describes research that has developed the principles of a modelling tool for the analytical evaluation of a manufacturing strategy. The appropriate process of manufacturing strategy formulation is based on mental synthesis with formal planning processes supporting this role. Inherent to such processes is a stage where the effects of alternative strategies on the performance of a manufacturing system must be evaluated so that a choice of preferred strategy can be made. Invariably this evaluation is carried out by practitioners applying mechanisms of judgement, bargaining and analysis. Ibis thesis makes a significant and original contribution to the provision of analytical support for practitioners in this role. The research programme commences by defining the requirements of analytical strategy evaluation from the perspective of practitioners. A broad taxonomy of models has been used to identify a set of potentially suitable techniques for the strategy evaluation task. Then, where possible, unsuitable modelling techniques have been identified on the basis of evidence in the literature and discarded from this set. The remaining modelling techniques have been critically appraised by testing representative contemporary modelling tools in an industrially based experimentation programme. The results show that individual modelling techniques exhibit various limitations in the strategy evaluation role, though some combinations do appear to provide the necessary functionality. On the basis of this comprehensive and in-depth knowledge a modelling tool ' has been specifically designed for this task. Further experimental testing has then been conducted to verify the principles of this modelling tool. Ibis research has bridged the fields of manufacturing strategy formulation and manufacturing systems modelling and makes two contributions to knowledge. Firstly, a comprehensive and in-depth platform of knowledge has been established about modelling techniques in manufacturing strategy evaluation. Secondly, the principles of a tool that supports this role have been formed and verified.

Modelling in the evaluation of a manufacturing strategy

This thesis describes research that has developed the principles of a modelling tool for the analytical evaluation of a manufacturing strategy. The appropriate process of manufacturing strategy formulation is based on mental synthesis with formal planning processes supporting this role. Inherent to such processes is a stage where the effects of alternative strategies on the performance of a manufacturing system must be evaluated so that a choice of preferred strategy can be made. Invariably this evaluation is carried out by practitioners applying mechanisms of judgement, bargaining and analysis. Ibis thesis makes a significant and original contribution to the provision of analytical support for practitioners in this role. The research programme commences by defining the requirements of analytical strategy evaluation from the perspective of practitioners. A broad taxonomy of models has been used to identify a set of potentially suitable techniques for the strategy evaluation task. Then, where possible, unsuitable modelling techniques have been identified on the basis of evidence in the literature and discarded from this set. The remaining modelling techniques have been critically appraised by testing representative contemporary modelling tools in an industrially based experimentation programme. The results show that individual modelling techniques exhibit various limitations in the strategy evaluation role, though some combinations do appear to provide the necessary functionality. On the basis of this comprehensive and in-depth knowledge a modelling tool ' has been specifically designed for this task. Further experimental testing has then been conducted to verify the principles of this modelling tool. Ibis research has bridged the fields of manufacturing strategy formulation and manufacturing systems modelling and makes two contributions to knowledge. Firstly, a comprehensive and in-depth platform of knowledge has been established about modelling techniques in manufacturing strategy evaluation. Secondly, the principles of a tool that supports this role have been formed and verified.

Modelling in the evaluation of a manufacturing strategy

This thesis describes research that has developed the principles of a modelling tool for the analytical evaluation of a manufacturing strategy. The appropriate process of manufacturing strategy formulation is based on mental synthesis with formal planning processes supporting this role. Inherent to such processes is a stage where the effects of alternative strategies on the performance of a manufacturing system must be evaluated so that a choice of preferred strategy can be made. Invariably this evaluation is carried out by practitioners applying mechanisms of judgement, bargaining and analysis. Ibis thesis makes a significant and original contribution to the provision of analytical support for practitioners in this role. The research programme commences by defining the requirements of analytical strategy evaluation from the perspective of practitioners. A broad taxonomy of models has been used to identify a set of potentially suitable techniques for the strategy evaluation task. Then, where possible, unsuitable modelling techniques have been identified on the basis of evidence in the literature and discarded from this set. The remaining modelling techniques have been critically appraised by testing representative contemporary modelling tools in an industrially based experimentation programme. The results show that individual modelling techniques exhibit various limitations in the strategy evaluation role, though some combinations do appear to provide the necessary functionality. On the basis of this comprehensive and in-depth knowledge a modelling tool ' has been specifically designed for this task. Further experimental testing has then been conducted to verify the principles of this modelling tool. Ibis research has bridged the fields of manufacturing strategy formulation and manufacturing systems modelling and makes two contributions to knowledge. Firstly, a comprehensive and in-depth platform of knowledge has been established about modelling techniques in manufacturing strategy evaluation. Secondly, the principles of a tool that supports this role have been formed and verified.

Evidence for CRHR1 in multiple sclerosis using supervised machine learning and meta-analysis in 12 566 individuals

The primary genetic risk factor in multiple sclerosis (MS) is the HLA-DRB1*1501 allele; however, much of the remaining genetic contribution to MS has yet to be elucidated. Several lines of evidence support a role for neuroendocrine system involvement in autoimmunity which may, in part, be genetically determined. Here, we comprehensively investigated variation within eight candidate hypothalamic-pituitary-adrenal (HPA) axis genes and susceptibility to MS. A total of 326 SNPs were investigated in a discovery dataset of 1343 MS cases and 1379 healthy controls of European ancestry using a multi-analytical strategy. Random Forests, a supervised machine-learning algorithm, identified eight intronic SNPs within the corticotrophin-releasing hormone receptor 1 or CRHR1 locus on 17q21.31 as important predictors of MS. On the basis of univariate analyses, six CRHR1 variants were associated with decreased risk for disease following a conservative correction for multiple tests. Independent replication was observed for CRHR1 in a large meta-analysis comprising 2624 MS cases and 7220 healthy controls of European ancestry. Results from a combined meta-analysis of all 3967 MS cases and 8599 controls provide strong evidence for the involvement of CRHR1 in MS. The strongest association was observed for rs242936 (OR = 0.82, 95% CI = 0.74-0.90, P = 9.7 × 10-5). Replicated CRHR1 variants appear to exist on a single associated haplotype. Further investigation of mechanisms involved in HPA axis regulation and response to stress in MS pathogenesis is warranted. © The Author 2010. Published by Oxford University Press. All rights reserved.

Psychological health and the risk of diabetes mellitus in Australian women: A 21-year prospective study

Background Symptoms of depression can be recurrent or limited to one episode. This study discusses the prospective association between psychological health, measured as change in depression symptoms, and the risk of diabetes mellitus in Australian women. Methods Data obtained from the Mater-University of Queensland Study of Pregnancy. Depression was measured using the Delusions-Symptoms: States Inventory. To examine possible transitions over time, depression was grouped into four categories and assessed at different phases over the 21-year period. Multiple logistic regression models and sensitivity analysis to assess the robustness of our analytical strategy were performed. Results Three hundred and one women reported diabetes 21 years after the index pregnancy. Almost one-third of the women who reported depression symptoms continued to report these at a subsequent follow-up (FU) phase. About 1 in 20 women who had not reported depression symptoms at the 5-year FU did so at the subsequent 14-year FU. In prospective analyses, we did not find a significant association between diabetes and negative change (not depressed to depressed, at subsequent phase); however, for women with positive history of symptoms of depression and women with persistent symptoms, there was a 1.97-fold (95% confidence interval [CI]: 1.14–3.40) to 2.23-fold (95% CI: 1.09–4.57) greater risk of diabetes. Conclusions Our study suggests that an increased risk of diabetes is significantly associated with persistent depression symptoms. It highlights the importance of recognizing depression symptoms in terms of women's psychological wellbeing and thus provides a basis for targeting those most at risk.

Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer

Improved sequencing technologies offer unprecedented opportunities for investigating the role of rare genetic variation in common disease. However, there are considerable challenges with respect to study design, data analysis and replication. Using pooled next-generation sequencing of 507 genes implicated in the repair of DNA in 1,150 samples, an analytical strategy focused on protein-truncating variants (PTVs) and a large-scale sequencing case-control replication experiment in 13,642 individuals, here we show that rare PTVs in the p53-inducible protein phosphatase PPM1D are associated with predisposition to breast cancer and ovarian cancer. PPM1D PTV mutations were present in 25 out of 7,781 cases versus 1 out of 5,861 controls (P = 1.12 × 10-5), including 18 mutations in 6,912 individuals with breast cancer (P = 2.42 × 10-4) and 12 mutations in 1,121 individuals with ovarian cancer (P = 3.10 × 10-9). Notably, all of the identified PPM1D PTVs were mosaic in lymphocyte DNA and clustered within a 370-base-pair region in the final exon of the gene, carboxy-terminal to the phosphatase catalytic domain. Functional studies demonstrate that the mutations result in enhanced suppression of p53 in response to ionizing radiation exposure, suggesting that the mutant alleles encode hyperactive PPM1D isoforms. Thus, although the mutations cause premature protein truncation, they do not result in the simple loss-of-function effect typically associated with this class of variant, but instead probably have a gain-of-function effect. Our results have implications for the detection and management of breast and ovarian cancer risk. More generally, these data provide new insights into the role of rare and of mosaic genetic variants in common conditions, and the use of sequencing in their identification.

To pave or not to pave: A social landscape analysis of land use decision-making in the towns of the lamprey watershed

Population pressure in coastal New Hampshire challenges land use decision-making and threatens the ecological health and functioning of Great Bay, an estuary designated as both a NOAA National Estuarine Research Reserve and an EPA National Estuary Program site. Regional population in the seacoast has quadrupled in four decades resulting in sprawl, increased impervious surface cover and larger lot rural development (Zankel, et.al., 2006). All of Great Bay’s contributing watersheds face these challenges, resulting in calls for strategies addressing growth, development and land use planning. The communities within the Lamprey River watershed comprise this case study. Do these towns communicate upstream and downstream when making land use decisions? Are cumulative effects considered while debating development? Do town land use groups consider the Bay or the coasts in their decision-making? This presentation, a follow-up from the TCS 2008 conference and a completed dissertation, will discuss a novel social science approach to analyze and understand the social landscape of land use decision-making in the towns of the Lamprey River watershed. The methods include semi-structured interviews with GIS based maps in a grounded theory analytical strategy. The discussion will include key findings, opportunities and challenges in moving towards a watershed approach for land use planning. This presentation reviews the results of the case study and developed methodology, which can be used in watersheds elsewhere to map out the potential for moving towns towards EBM and watershed-scaled, land use planning. (PDF contains 4 pages)

Laser desorption/ionization mass spectrometry on porous silicon for metabolome analyses: influence of surface oxidation

Jenkins, Tudor; Vaidyanathan, S.; Jones, D.G.; Ellis, J., (2007) 'Laser desorption/ionization mass spectrometry on porous silicon for metabolome analyses: influence of surface oxidation', Rapid Communications in Mass Spectrometry 21(13) pp.2157-2166 RAE2008

De novo sequencing of two novel peptides homologous to calcitonin-like peptides, from skin secretion of the Chinese Frog, Odorrana schmackeri

An MS/MS based analytical strategy was followed to solve the complete sequence of two new peptides from frog (Odorrana schmackeri) skin secretion. This involved reduction and alkylation with two different alkylating agents followed by high resolution tandem mass spectrometry. De novo sequencing was achieved by complementary CID and ETD fragmentations of full-length peptides and of selected tryptic fragments. Heavy and light isotope dimethyl labeling assisted with annotation of sequence ion series. The identified primary structures are GCD[I/L]STCATHN[I/L]VNE[I/L]NKFDKSKPSSGGVGPESP-NH2 and SCNLSTCATHNLVNELNKFDKSKPSSGGVGPESF-NH2, i.e. two carboxyamidated 34 residue peptides with an aminoterminal intramolecular ring structure formed by a disulfide bridge between Cys2 and Cys7. Edman degradation analysis of the second peptide positively confirmed the exact sequence, resolving I/L discriminations. Both peptide sequences are novel and share homology with calcitonin, calcitonin gene related peptide (CGRP) and adrenomedullin from other vertebrates. Detailed sequence analysis as well as the 34 residue length of both O. schmackeri peptides, suggest they do not fully qualify as either calcitonins (32 residues) or CGRPs (37 amino acids) and may justify their classification in a novel peptide family within the calcitonin gene related peptide superfamily. Smooth muscle contractility assays with synthetic replicas of the S–S linked peptides on rat tail artery, uterus, bladder and ileum did not reveal myotropic activity.

Identification de nouveaux substrats des kinases Erk1/2 par une approche bio-informatique, pharmacologique et phosphoprotéomique

La phosphorylation est une modification post-traductionnelle omniprésente des protéines Cette modification est ajoutée et enlevée par l’activité enzymatique respective des protéines kinases et phosphatases. Les kinases Erk1/2 sont au cœur d’une voie de signalisation importante qui régule l’activité de protéines impliquées dans la traduction, le cycle cellulaire, le réarrangement du cytosquelette et la transcription. Ces kinases sont aussi impliquées dans le développement de l’organisme, le métabolisme du glucose, la réponse immunitaire et la mémoire. Différentes pathologies humaines comme le diabète, les maladies cardiovasculaires et principalement le cancer, sont associées à une perturbation de la phosphorylation sur les différents acteurs de cette voie. Considérant l’importance biologique et clinique de ces deux kinases, connaître l’étendue de leur activité enzymatique pourrait mener au développement de nouvelles thérapies pharmacologiques. Dans ce contexte, l’objectif principal de cette thèse était de mesurer l’influence de cette voie sur le phosphoprotéome et de découvrir de nouveaux substrats des kinases Erk1/2. Une étude phosphoprotéomique de cinétique d’inhibition pharmacologique de la voie de signalisation Erk1/2 a alors été entreprise. Le succès de cette étude était basé sur trois technologies clés, soit l’enrichissement des phosphopeptides avec le dioxyde de titane, la spectrométrie de masse haut débit et haute résolution, et le développement d’une plateforme bio-informatique nommée ProteoConnections. Cette plateforme permet d’organiser les données de protéomique, évaluer leur qualité, indiquer les changements d’abondance et accélérer l’interprétation des données. Une fonctionnalité distinctive de ProteoConnections est l’annotation des sites phosphorylés identifiés (kinases, domaines, structures, conservation, interactions protéiques phospho-dépendantes). Ces informations ont été essentielles à l’analyse des 9615 sites phosphorylés sur les 2108 protéines identifiées dans cette étude, soit le plus large ensemble rapporté chez le rat jusqu’à ce jour. L’analyse des domaines protéiques a révélé que les domaines impliqués dans les interactions avec les protéines, les acides nucléiques et les autres molécules sont les plus fréquemment phosphorylés et que les sites sont stratégiquement localisés pour affecter les interactions. Un algorithme a été implémenté pour trouver les substrats potentiels des kinases Erk1/2 à partir des sites identifiés selon leur motif de phosphorylation, leur cinétique de stimulation au sérum et l’inhibition pharmacologique de Mek1/2. Une liste de 157 substrats potentiels des kinases Erk1/2 a ainsi été obtenue. Parmi les substrats identifiés, douze ont déjà été rapportés et plusieurs autres ont des fonctions associées aux substrats déjà connus. Six substrats (Ddx47, Hmg20a, Junb, Map2k2, Numa1, Rras2) ont été confirmés par un essai kinase in vitro avec Erk1. Nos expériences d’immunofluorescence ont démontré que la phosphorylation de Hmg20a sur la sérine 105 par Erk1/2 affecte la localisation nucléocytoplasmique de cette protéine. Finalement, les phosphopeptides isomériques positionnels, soit des peptides avec la même séquence d’acides aminés mais phosphorylés à différentes positions, ont été étudiés avec deux nouveaux algorithmes. Cette étude a permis de déterminer leur fréquence dans un extrait enrichi en phosphopeptides et d’évaluer leur séparation par chromatographie liquide en phase inverse. Une stratégie analytique employant un des algorithmes a été développée pour réaliser une analyse de spectrométrie de masse ciblée afin de découvrir les isomères ayant été manqués par la méthode d’analyse conventionnelle.

Research plan discussion: The socio-technical construction of MOOCs and educator practices in HE

In this seminar slot, we will discuss Steve's research aims and plan. Massive open online courses (MOOCs) have received substantial coverage in mainstream sources, academic media, and scholarly journals, both negative and positive. Numerous articles have addressed their potential impact on Higher Education systems in general, and some have highlighted problems with the instructional quality of MOOCs, and the lack of attention to research from online learning and distance education literature in MOOC design. However, few studies have looked at the relationship between social change and the construction of MOOCs within higher education, particularly in terms of educator and learning designer practices. This study aims to use the analytical strategy of Socio-Technical Interaction Networks (STIN) to explore the extent to which MOOCs are socially shaped and their relationship to educator and learning designer practices. The study involves a multi-site case study of 3 UK MOOC-producing universities and aims to capture an empirically based, nuanced understanding of the extent to which MOOCs are socially constructed in particular contexts, and the social implications of MOOCs, especially among educators and learning designers.

Reconstruction of in vivo time-evolving neuroendocrine dose - response properties unveils admixed deterministic and stochastic elements

Homeostasis in the intact organism is achieved implicitly by repeated incremental feedback (inhibitory) and feedforward (stimulatory) adjustments enforced via intermittent signal exchange. In separated systems, neurohormone signals act deterministically on target cells via quantifiable effector-response functions. On the other hand, in vivo interglandular signaling dynamics have not been estimable to date. Indeed, experimentally isolating components of an interactive network definitionally disrupts time-sensitive linkages. We implement and validate analytical reconstruction of endogenous effector-response properties via a composite model comprising (i) a deterministic basic feedback and feedforward ensemble structure; (ii) judicious statistical allowance for possible stochastic variability in individual biologically interpretable dose–response properties; and (iii) the sole data requirement of serially observed concentrations of a paired signal (input) and response (output). Application of this analytical strategy to a prototypical neuroendocrine axis in the conscious uninjected horse, sheep, and human (i) illustrates probabilistic estimation of endogenous effector dose–response properties; and (ii) unmasks statistically vivid (2- to 5-fold) random fluctuations in inferred target-gland responsivity within any given pulse train. In conclusion, balanced mathematical formalism allows one to (i) reconstruct deterministic properties of interglandular signaling in the intact mammal and (ii) quantify apparent signal-response variability over short time scales in vivo. The present proof-of-principle experiments introduce a previously undescribed means to estimate time-evolving signal-response relationships without isotope infusion or pathway disruption.

Desafios do Programa HIPERDIA e implicações para a enfermagem

INTRODUÇÃO: O Programa HIPERDIA foi implantado em 2001 na atenção básica devido à gravidade epidemiológica da Hipertensão Arterial Sistêmica (HAS) e o Diabetes Mellitus (DM), afecções que podem acarretar sérias complicações incutindo limitações e sofrimento na vida de seus portadores e suas famílias. Nesse contexto, ressalte-se a importância da prevenção primária dessas afecções e de suas complicações. Passado mais de uma década de sua implementação, cabe refletir acerca do impacto nas condições de saúde que o Programa tem gerado entre seus usuários. OBJETIVOS: Elucidar os princípios, a filosofia e a política norteadora do Programa HIPERDIA do Ministério da Saúde (MS); descrever como funciona o atendimento do usuário pela equipe de saúde de um Programa HIPERDIA; explorar os comportamentos de vida e saúde demonstrados pelos usuários do HIPERDIA após sua inserção no Programa. DESCRIÇÃO METODOLÓGICA: Trata-se de um Estudo de Caso segundo Yin (2010) cujo objeto de estudo foi um Programa HIPERDIA executado numa Unidade Básica de Saúde da periferia de Belém-PA. Os dados foram obtidos por meio de entrevista com usuários, equipe e gestores do Programa, além da observação direta do campo, consulta de prontuários e da documentação oficial do MS. A análise dos dados obtidos foi feita por meio da estratégia analítica “Contando com Proposições Teóricas” e da técnica analítica “Combinação de Padrão”. RESULTADOS: A precarização da gestão do Programa HIPERDIA ilustrada por deficiências na infraestrutura, insumos, medicamentos e fragilidades na rede de referência e contrarreferência, a demanda espontânea excessiva que sobrecarrega a equipe de saúde alocada em número insuficiente e o contexto de pobreza e violência urbana em que os usuários vivem contribuem para a baixa adesão ao regime terapêutico e limitam a equipe em sua atuação interdisciplinar e integral. Ademais, o modelo de atenção vigente é pautado no tradicional, baseado em consultas e prescrições e que não tem se demonstrado suficiente para atender integralmente às necessidades de atenção ao portador de condição crônica, que requer cuidados prolongados com adoção de estilos de vida mais condizentes e saudáveis. CONSIDERAÇÕES FINAIS: Grandes desafios se desenham diante dos dados emergidos deste estudo e envolvem ações macrogovernamentais e intersetoriais que promovam melhorias nas condições de vida da população o que requer vontade política para investimento dos recursos necessários. Não obstante a isso, a enfermagem pode dar sua contribuição promovendo cuidado cultural e ações de autocuidado, personalizando o plano de ação e trazendo a corresponsabilidade do usuário e sua família na melhoria de sua condição de saúde.