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The In Utero Programming Effect of Increased Maternal Androgens and a Direct Fetal Intervention on Liver and Metabolic Function in Adult Sheep
Kirsten Hogg, Charlotte Wood, Alan S. McNeilly, W. Colin Duncan
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024877
Abstract: Epigenetic changes in response to external stimuli are fast emerging as common underlying causes for the pre-disposition to adult disease. Prenatal androgenization is one such model that results in reproductive and metabolic features that are present in conditions such as polycystic ovary syndrome (PCOS). We examined the effect of prenatal androgens on liver function and metabolism of adult sheep. As non-alcoholic fatty liver disease is increased in PCOS we hypothesized that this, and other important liver pathways including metabolic function, insulin–like growth factor (IGF) and steroid receptivity, would be affected. Pregnant ewes received vehicle control (C; n = 5) or testosterone propionate (TP; n = 9) twice weekly (100 mg; i.m) from d62–102 (gestation 147 days). In a novel treatment paradigm, a second cohort received a direct C (n = 4) or TP (20 mg; n = 7) fetal injection at d62 and d82. In adults, maternal TP exposure resulted in increased insulin secretion to glucose load (P<0.05) and the histological presence of fatty liver (P<0.05) independent of central obesity. Additionally, hepatic androgen receptor (AR; P<0.05), glucocorticoid receptor (GR; P<0.05), UDP- glucose ceramide glucosyltransferase (UGCG; P<0.05) and IGF1 (P<0.01) expression were upregulated. The direct fetal intervention (C and TP) led to early fatty liver changes in all animals without differential changes in insulin secretion. Furthermore, hepatic phosphoenolpyruvate carboxykinase (PEPCK) was up-regulated in the fetal controls (P<0.05) and this was opposed by fetal TP (P<0.05). Hepatic estrogen receptor (ERα; P<0.05) and mitogen activated protein kinase kinase 4 (MAP2K4; P<0.05) were increased following fetal TP exposure. Adult liver metabolism and signaling can be altered by early exposure to sex steroids implicating epigenetic regulation of metabolic disturbances that are common in PCOS.
Early Onset Pre-Eclampsia Is Associated with Altered DNA Methylation of Cortisol-Signalling and Steroidogenic Genes in the Placenta
Kirsten Hogg, John D. Blair, Deborah E. McFadden, Peter von Dadelszen, Wendy P. Robinson
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0062969
Abstract: Placental cortisol is inactivated in normotensive pregnancies, but is frequently present in pre-eclampsia associated placentae. Since glucocorticoids are strongly associated with the programming of long-term health, we assessed DNA methylation of genes involved in cortisol signalling and bioavailability, and hormonal signalling in the placenta of normotensive and hypertensive pregnancies. Candidate genes/CpG sites were selected through analysis of Illumina Infinium HumanMethylation450 BeadChip array data on control (n = 19) and early onset pre-eclampsia (EOPET; n = 19) placental samples. DNA methylation was further quantified by bisulfite pyrosequencing in a larger cohort of control (n = 111) cases, in addition to EOPET (n = 19), late onset pre-eclampsia (LOPET; n = 18) and normotensive intrauterine growth restriction (nIUGR; n = 13) cases. DNA methylation (percentage points) was increased at CpG sites within genes encoding the glucocorticoid receptor (NR3C1 exon 1D promoter; +8.46%; P<0.01) and corticotropin releasing hormone (CRH) binding protein (CRHBP intron 3; +9.14%; P<0.05), and decreased within CRH (5′ UTR; ?4.30%; P = 0.11) in EOPET-associated placentae, but not in LOPET nor nIUGR cases, compared to controls. Differential DNA methylation was not observed among groups at the 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) gene promoter. Significant hypomethylation was observed in pre-eclampsia but not nIUGR placentae for steroidogenic genes, including CYP11A1 (exon1; EOPET; ?9.66%; P<0.00001, and LOPET; ?5.77%; P<0.001), 3β-hydroxy-delta-5-steroid dehydrogenase type 1 (HSD3B1 exon 2; EOPET; ?12.49%; P<0.00001, and LOPET; ?6.88%; P<0.001), TEA domain family member 3 (TEAD3 intron 1; EOPET; ?12.56%; P<0.00001) and CYP19 (placental-specific exon 1.1 promoter; EOPET; ?10.62%, P<0.0001). These data represent dysregulation of the placental epigenome in pre-eclampsia related to genes involved in maintaining the hormonal environment during pregnancy and highlights particular susceptibility in the early onset syndrome.
Water and the Configuration of Social Worlds: An Anthropological Perspective  [PDF]
Kirsten Hastrup
Journal of Water Resource and Protection (JWARP) , 2013, DOI: 10.4236/jwarp.2013.54A009

From an anthropological perspective, water is not only the sine qua non of life in general, it is also seen to configure societies in particular ways, and to generate particular values. This will be substantiated in four moves. First, the hydrological cycle and other elementals of water will be discussed. Second, we shall zoom in on rivers, transforming natural resources and social communities as they bend and twist. Third, we shall discuss artificially established canals, emulating natural flows, but having their own long-term social and political implications. Fourth, we shall focus on wells, providing nodal points of social life and potential conflict. The article ends with some observations on water as a theory-machine.

The Pancreas Is Altered by In Utero Androgen Exposure: Implications for Clinical Conditions Such as Polycystic Ovary Syndrome (PCOS)
Mick Rae, Cathal Grace, Kirsten Hogg, Lisa Marie Wilson, Sophie L. McHaffie, Seshadri Ramaswamy, Janis MacCallum, Fiona Connolly, Alan S. McNeilly, Colin Duncan
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0056263
Abstract: Using an ovine model of polycystic ovary syndrome (PCOS), (pregnant ewes injected with testosterone propionate (TP) (100 mg twice weekly) from day (d)62 to d102 of d147 gestation (maternal injection – MI-TP)), we previously reported female offspring with normal glucose tolerance but hyperinsulinemia. We therefore examined insulin signalling and pancreatic morphology in these offspring using quantitative (Q) RT-PCR and western blotting. In addition the fetal pancreatic responses to MI-TP, and androgenic and estrogenic contributions to such responses (direct fetal injection (FI) of TP (20 mg) or diethylstilbestrol (DES) (20 mg) at d62 and d82 gestation) were assessed at d90 gestation. Fetal plasma was assayed for insulin, testosterone and estradiol, pancreatic tissue was cultured, and expression of key β-cell developmental genes was assessed by QRT-PCR. In female d62MI-TP offspring insulin signalling was unaltered but there was a pancreatic phenotype with increased numbers of β-cells (P<0.05). The fetal pancreas expressed androgen receptors in islets and genes involved in β-cell development and function (PDX1, IGF1R, INSR and INS) were up-regulated in female fetuses after d62MI-TP treatment (P<0.05–0.01). In addition the d62MI-TP pancreas showed increased insulin secretion under euglycaemic conditions (P<0.05) in vitro. The same effects were not seen in the male fetal pancreas or when MI-TP was started at d30, before the male programming window. As d62MI-TP increased both fetal plasma testosterone (P<0.05) and estradiol concentrations (P<0.05) we assessed the relative contribution of androgens and estrogens. FI-TP (commencing d62) (not FI-DES treatment) caused elevated basal insulin secretion in vitro and the genes altered by d62MI-TP treatment were similarly altered by FI-TP but not FI-DES. In conclusion, androgen over-exposure alters fetal pancreatic development and β-cell numbers in offspring. These data suggest that that there may be a primary pancreatic phenotype in models of PCOS, and that there may be a distinct male and female pancreas.
Directing Dissent: Governing Political Dissidence in Spanish Prisons
Alison Hogg
O?ati Socio-Legal Series , 2012,
Abstract: Under article 25.2 Spanish Constitution the incarceration of a person should aim to re-educate and socially rehabilitate. Along the same line, Art. 59.2 of the General Penitentiary Law (GPL) of 21 September 1979 asserts that treatment in prisons, should aim to motivate the incarcerated to become law abiding and to respect themselves, their family, peers, and society. This is allegedly achieved by them serving their sentences under conditions that reflect their individualised scientific grade (Art. 72 GPL). How do these aims translate into practice for a group of individuals, ETA members, condemned for offences committed in reaction to a perceived oppressive majoritarianism? It is hypothesized that the Spanish state either rehabilitates the deviants thus showing them the error of their ways and directs them to normality through a highly individualised assessment based on politically constructed common factors, or contain and civically and politically exclude those who resist. A Foucauldian approach is used to analyse the mechanisms of power and, the security and penal apparatuses erected to manage and discipline this collective, more precisely of governmentality, normalisation, and of biopower. Particular attention is paid to the techniques used to ‘normalise’ and govern this collective. At first sight, one would think that only disciplinary mechanisms in a penitentiary setting need be used to achieve the earlier stated aims given that they have a ‘captive audience’; however, in reaction to an intransigent collective with an embedded political praxis , the State has adopted a hybridised system of power. The system combines individual and collective security mechanisms, and legal instruments to achieve this objective. In managing risk, the Spanish penal apparatus has adopted strategies that involve politically and civically castrating those that are deemed too high a risk and incorrigible. DOWNLOAD THIS PAPER FROM SSRN: http://ssrn.com/abstract=1991742
The privatisation of non-custodial measures: an uneasy balance between legitimacy and immediacy
Alison Hogg
O?ati Socio-Legal Series , 2012,
Abstract: All developed countries with few exceptions are facing problems related to prison overpopulation and non-custodial measures are marketed as the solution. The public’s involvement and endorsement of non-custodial measures is imperative and the success of these measures will depend upon the contribution of the private sector. The private for-profit and non-profit sectors’ involvement in this area is not new and unlikely to decrease; however, the public sector must be the one to identify the needs and not fall victim to the courting of the private for-profit sector, which prioritises profit and for who the offender in this context has become a commodity. The non-profit sector can counter the effects of risk management and its plethora of requirements, which are partly responsible for increasing technical violations and obliging probation to take on a more adversarial role. Up until our expectations of probation and offenders in the community become more attainable and reflexive, the non-profit sector can temper the depersonalised and automatic feedback. The legitimacy of non-custodial measures depends upon them being cost-effective, efficient, socially acceptable and reflexive. This paper focuses on three genres of non-custodial sentences, which are characteristic of retribution, coercive treatment and restorative justice. The use of these in the United States, Canada, England and Wales, Sweden and Spain is briefly overviewed as well as the contribution of the private sector. Non-custodial measures aren’t the panacea for all offending in all cultures but surely are a step in the right direction. La mayoría de los países desarrollados se enfrentan a problemas relacionados con la sobrepoblación de las cárceles. Las medidas no privativas de libertad se presentan como una solución a este problema. Es necesario que la opinión pública participe y apruebe las medidas no privativas; el éxito de estas medidas dependerá también de la aportación del sector privado. La participación del sector privado, tanto de organizaciones con ánimo de lucro, como sin ánimo de lucro, en esta área no es nueva y es improbable que disminuya; sin embargo, el sector público debe identificar las necesidades sin dejarse influenciar por el sector privado con ánimo de lucro, interesado en obtener un beneficio económico, convirtiendo a los presos en una mercancía. Las organizaciones sin ánimo de lucro pueden contrarrestar los efectos de la gestión de riesgos y sus numerosos requisitos, que son en parte responsables del aumento de los incumplimientos técnicos y de que la libertad condicional a
Application of Groupthink to Generation Y Decision Making Processes within a Professional Services Context in New Zealand
David Hogg
International Journal of Business and Management , 2013, DOI: 10.5539/ijbm.v8n8p69
Abstract: Many organisations are adjusting to the presence of Generation Y and their values. Industries that have large annual intakes of employees, like Professional Services, find this adjustment particularly challenging. Generation Y challenges workplace rules and norms, this article seeks to understand the decision making process used by Generation Y to form expectations and perceptions in relation to workplace rules and norms. Understanding this process will help organisations to better educate and influence Generation Y regarding their career choices and conduct within the workplace. This article will focus on applying the Groupthink theory to explain the decision making process used by Generation Y to form expectations and perceptions in relation to workplace rules and norms. In the conclusion an adjusted Groupthink Model that applies specifically to this context is presented. Lessons for organisations that may want to have greater influence over the decision making process used by Generation Y are also presented.
Quantum Computing and Phase Transitions in Combinatorial Search
Tad Hogg
Physics , 1995,
Abstract: We introduce an algorithm for combinatorial search on quantum computers that is capable of significantly concentrating amplitude into solutions for some NP search problems, on average. This is done by exploiting the same aspects of problem structure as used by classical backtrack methods to avoid unproductive search choices. This quantum algorithm is much more likely to find solutions than the simple direct use of quantum parallelism. Furthermore, empirical evaluation on small problems shows this quantum algorithm displays the same phase transition behavior, and at the same location, as seen in many previously studied classical search methods. Specifically, difficult problem instances are concentrated near the abrupt change from underconstrained to overconstrained problems.
A Framework for Structured Quantum Search
Tad Hogg
Physics , 1997, DOI: 10.1016/S0167-2789(98)00047-5
Abstract: A quantum algorithm for general combinatorial search that uses the underlying structure of the search space to increase the probability of finding a solution is presented. This algorithm shows how coherent quantum systems can be matched to the underlying structure of abstract search spaces, and is analytically simpler than previous structured search methods. The algorithm is evaluated empirically with a variety of search problems, and shown to be particularly effective for searches with many constraints. Furthermore, the algorithm provides a simple framework for utilizing search heuristics. It also exhibits the same phase transition in search difficulty as found for sophisticated classical search methods, indicating it is effectively using the problem structure.
A Framework for Quantum Search Heuristics
Tad Hogg
Physics , 1996,
Abstract: A quantum algorithm for combinatorial search is presented that provides a simple framework for utilizing search heuristics. The algorithm is evaluated in a new case that is an unstructured version of the graph coloring problem. It performs significantly better than the direct use of quantum parallelism, on average, in cases corresponding to previously identified phase transitions in search difficulty. The conditions underlying this improvement are described. Much of the algorithm is independent of particular problem instances, making it suitable for implementation as a special purpose device.
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