Trace elements as predictors of preeclampsia in type 1 diabetic pregnancy

Preeclampsia (PE) affects approximately 5% of all pregnancies, but is increased several-fold in women with pre-gestational type 1 diabetes mellitus (T1DM). Increased oxidative stress and altered maternal plasma trace elements that modulate the antioxidant system have been implicated in PE. In non-diabetic women, increased plasma copper and iron and decreased manganese, selenium, and zinc have been associated with PE in cross-sectional studies. In a longitudinal study, we hypothesized that plasma levels of trace elements differ between T1DM women with vs. without subsequent PE. Samples were collected during the first (gestation 12.2 ± 1.9 weeks, [mean ± SD]), second (21.6 ± 1.5 weeks), and third (31.5 ± 1.7 weeks) trimesters of pregnancy, all before the onset of PE. We compared 23 T1DM women who subsequently developed PE with 24 T1DM women who remained normotensive; and we included 19 non-diabetic (non-DM) normotensive pregnant women as reference controls. Trace elements were measured using inductively coupled plasma mass spectroscopy. In T1DM women with subsequent PE vs normotensive, only plasma zinc was significantly higher at the first trimester, while copper:zinc and copper:high-density lipoprotein cholesterol ratios were higher throughout gestation (all P < .05). These findings persisted after adjustment for covariates. Higher copper:zinc ratios may contribute to oxidative stress in T1DM women who develop PE. Ratios of pro- to anti-oxidant factors may predict risk for PE in diabetic pregnancies more effectively than individual trace element levels.

Global identification of androgen response elements

Chromatin immunoprecipitation (ChIP) is an invaluable tool in the study of transcriptional regulation. ChIP methods require both a priori knowledge of the transcriptional regulators which are important for a given biological system and high-quality specific antibodies for these targets. The androgen receptor (AR) is known to play essential roles in male sexual development, in prostate cancer and in the function of many other AR-expressing cell types (e.g. neurons and myocytes). As a ligand-activated transcription factor the AR also represents an endogenous, inducible system to study transcriptional biology. Therefore, ChIP studies of the AR can make use of treatment contrast experiments to define its transcriptional targets. To date several studies have mapped AR binding sites using ChIP in combination with genome tiling microarrays (ChIP-chip) or direct sequencing (ChIP-seq), mainly in prostate cancer cell lines and with varying degrees of genomic coverage. These studies have provided new insights into the DNA sequences to which the AR can bind, identified AR cooperating transcription factors, mapped thousands of potential AR regulated genes and provided insights into the biological processes regulated by the AR. However, further ChIP studies will be required to fully characterise the dynamics of the AR-regulated transcriptional programme, to map the occupancy of different AR transcriptional complexes which result in different transcriptional output and to delineate the transcriptional networks downstream of the AR.

Improving composite damage modelling through automatic placement of cohesive elements

Numerous experimental studies of damage in composite laminates have shown that intralaminar (in-plane) matrix cracks lead to interlaminar delamination (out-of-plane) at ply interfaces. The smearing of in-plane cracks over a volume, as a consequence of the use of continuum damage mechanics, does not always effectively capture the full extent of the interaction between the two failure mechanisms. A more accurate representation is obtained by adopting a discrete crack approach via the use of cohesive elements, for both in-plane and out-of-plane damage. The difficulty with cohesive elements is that their location must be determined a priori in order to generate the model; while ideally the position of the crack migration, and more generally the propagation path, should be obtained as part of the problem’s solution. With the aim of enhancing current modelling capabilities with truly predictive capabilities, a concept of automatic insertion of interface elements is utilized. The consideration of a simple traction criterion in relation to material strength, evaluated at each node of the model (or of the regions of the model where it is estimated cracks might form), allows for the determination of initial crack location and subsequent propagation by the insertion of cohesive elements during the course of the analysis. Several experimental results are modelled using the commercial package ABAQUS/Standard with an automatic insertion subroutine developed in this work, and the results are presented to demonstrate the capabilities of this technique.

Streaming Elements for FPGA Signal and Image Processing Accelerators

Field programmable gate array devices boast abundant resources with which custom accelerator components for signal, image and data processing may be realised; however, realising high performance, low cost accelerators currently demands manual register transfer level design. Software-programmable ’soft’ processors have been proposed as a way to reduce this design burden but they are unable to support performance and cost comparable to custom circuits. This paper proposes a new soft processing approach for FPGA which promises to overcome this barrier. A high performance, fine-grained streaming processor, known as a Streaming Accelerator Element, is proposed which realises accelerators as large scale custom multicore networks. By adopting a streaming execution approach with advanced program control and memory addressing capabilities, typical program inefficiencies can be almost completely eliminated to enable performance and cost which are unprecedented amongst software-programmable solutions. When used to realise accelerators for fast fourier transform, motion estimation, matrix multiplication and sobel edge detection it is shown how the proposed architecture enables real-time performance and with performance and cost comparable with hand-crafted custom circuit accelerators and up to two orders of magnitude beyond existing soft processors.

Compositonal Analysis of Potentially harmful Elements in Soils: Implications for Epidemiology and Kidney Disease

A substantial proportion of aetiological risks for many cancers and chronic diseases remain unexplained. Using geochemical soil and stream water samples collected as part of the Tellus Project studies, current research is investigating naturally occurring background levels of potentially toxic elements (PTEs) in soils and stream sediments and their possible relationship with progressive chronic kidney disease (CKD). The Tellus geological mapping project, Geological Survey Northern Ireland, collected soil sediment and stream water samples on a grid of one sample site every 2 km2 across the rural areas of Northern Ireland resulting in an excess of 6800 soil sampling locations and more than 5800 locations for stream water sampling. Accumulation of several PTEs including arsenic, cadmium, chromium, lead and mercury have been linked with human health and implicated in renal function decline. The hypothesis is that long-term exposure will result in cumulative exposure to PTEs and act as risk factor(s) for cancer and diabetes related CKD and its progression. The ‘bioavailable’ fraction of total PTE soil concentration depends on the ‘bioaccessible’ proportion through an exposure pathway. Recent work has explored this bioaccessible fraction for a range of PTEs across Northern Ireland. In this study the compositional nature of the multivariate geochemical PTE variables and bioaccessible data is explored to augment the investigation into the potential relationship between PTEs, bioaccessibility and disease data.

Assessing elements of a family approach to reduce adolescent drinking frequency: parent-adolescent relationship, knowledge management, and keeping secrets

AIMS: To estimate 1) the associations between parent-adolescent relationship, parental knowledge and subsequent adolescent drinking frequency and 2) the influence of alcohol use on parental knowledge.

DESIGN: Path analysis of school based cohort study with annual surveys SETTING: Post primary schools from urban and intermediate/rural areas in Northern Ireland PARTICIPANTS: 4,937 post primary school students aged around 11 years in 2000 followed until around age 16 in 2005.

MEASUREMENTS: Pupil reported measures of: frequency of alcohol use; parental-child relationship quality; sub-dimensions of parental monitoring: parental control, parental solicitation, child disclosure and child secrecy.

FINDINGS: Higher levels of parental control (Ordinal logistic OR 0.86 95% CI 0.78, 0.95) and lower levels of child secrecy (OR 0.83 95% CI 0.75 0.92) were associated with less frequent alcohol use subsequently. Parental solicitation and parent-child relationship quality were not associated with drinking frequency. Weekly alcohol drinking was associated with higher subsequent secrecy (Beta -0.42 95% CI -0.53, -0.32) and lower parental control (Beta -0.15 95% CI -0.26, -0.04). Secrecy was more strongly predictive of alcohol use at younger compared with older ages (P=0.02), and alcohol use was less strongly associated with parental control among families with poorer relationships (P=0.04).

CONCLUSIONS: Adolescent alcohol use appears to increase as parental control decreases and child secrecy increases. Greater parental control is associated with less frequent adolescent drinking subsequently, while parent-child attachment and parental solicitation have little influence on alcohol use. 

Endothelial Function in Hypertension: Victim or Culprit?

Far from simply lining the inner surface of blood vessels, the cellular monolayer that comprises the endothelium is a highly active organ that regulates vascular tone. In health, the endothelium maintains the balance between opposing dilator and constrictor influences, while in disease, it is the common ground on which cardiovascular risk factors act to initiate the atherosclerotic process. As such, it is the site at which cardiovascular disease begins and consequently acts as a barometer of an individual's likely future cardiovascular health. The vascular endothelium is a very active organ responsible for the regulation of vascular tone through the effects of locally synthesized mediators, predominantly nitric oxide (NO), endothelial NO synthase (eNOS), and superoxide. NO is abundantly evident in normally functioning vasculature where it acts as a vasodilator, inhibits inflammation, and has an antiaggregant effect on platelets. Its depletion is both a sign and cause of endothelial dysfunction resulting from reduced activity of eNOS and amplified production of nicotinamide adenine dinucleotide oxidase, which, in turn, results in raised levels of reactive oxygen species. This cascade is the basis for reduced vascular compliance through an imbalanced regulation of tone with a predominance of vasoconstrictive elements. Further, structural changes in the microvasculature are a critical early step in the loss of normal function. This microvascular dysfunction is known to be highly predictive of future macrovascular events and is consequently a very attractive target for intervention in the hypertensive population in order to prevent cardiovascular events.

Generalized collisional radiative model for light elements: C: Data for the B isonuclear sequence

A first stage collision database is assembled which contains electron-impact excitation, ionization,\r and recombination rate coefficients for B, B + , B 2+ , B 3+ , and B 4+ . The first stage database\r is constructed using the R-matrix with pseudostates, time-dependent close-coupling, and perturbative\r distorted-wave methods. A second stage collision database is then assembled which contains\r generalized collisional-radiative ionization, recombination, and power loss rate coefficients as a\r function of both temperature and density. The second stage database is constructed by solution of\r the collisional-radiative equations in the quasi-static equilibrium approximation using the first\r stage database. Both collision database stages reside in electronic form at the IAEA Labeled Atomic\r Data Interface (ALADDIN) database and the Atomic Data Analysis Structure (ADAS) open database.

Generalized collisional radiative model for light elements. Part B: Data for the Be isonuclear sequence

A first-stage collision database is assembled which contains electron-impact excitation, ionization, and recombination rate coefficients for Be, Be+, Be2+, and Be3+. The first-stage database is constructed using the R-matrix with pseudo-states, time-dependent close-coupling, and perturbative, distorted-wave methods. A second-stage collision database is then assembled which contains generalized collisional-radiative and radiated power loss coefficients. The second-stage database is constructed by solution of collisional-radiative equations in the quasi-static equilibrium approximation using the first-stage database. Both collision database stages reside in electronic form at the ORNL Controlled Fusion Atomic Data Center and in the ADAS database, and are easily accessed over the worldwide internet. © 2007 Elsevier Inc. All rights reserved.

Generalised collisional-radiative model for light elements. A: Data for the Li isonuclear sequence

A first stage collision database is assembled which contains electron-impact effective collision strengths, and ionization and recombination rate coefficients for Li, Li+, and Li2+. The first stage database is constructed using the R-matrix with pseudo-states, time-dependent close-coupling, converged close-coupling, and perturbative distorted-wave methods. A second stage collision database is then assembled which contains generalized collisional-radiative and radiated power loss coefficients. The second stage database is constructed by solution of collisional-radiative equations in the quasi-static equilibrium approximation using the first stage database. Both collision database stages reside in electronic form at the ORNL Controlled Fusion Atomic Data Center and in the ADAS database, and are easily accessed over the worldwide internet. ?? 2006 Elsevier Inc. All rights reserved.

Cyclic behaviour of RC elements with plain reinforcing bars

O comportamento cíclico das estruturas de betão armado é fortemente condicionado pelo mecanismo de aderência entre o betão e o aço. O escorregamento relativo entre os dois materiais, resultante da degradação progressiva da aderência em elementos solicitados por ações cíclicas, é uma causa frequente de danos graves e até do colapso de estruturas devido à ocorrência de sismos. Entre as estruturas existentes de betão armado que foram dimensionadas e construídas antes da entrada em vigor dos regulamentos sísmicos atuais, muitas foram construídas com armadura lisa, e portanto, possuem fracas propriedades de aderência. A informação disponível na literatura sobre o comportamento cíclico de elementos estruturais de betão armado com armadura lisa é reduzida e a influência das propriedades da aderência associadas a este tipo de armadura no comportamento cíclico das estruturas existentes não se encontra ainda devidamente estudada. O objectivo principal desta tese foi estudar a influência do escorregamento na resposta cíclica de elementos estruturais de betão armado com armadura lisa. Foram realizados ensaios cíclicos em elementos do tipo nó viga-pilar, construídos à escala real, representativos de ligações interiores em edifícios existentes sem pormenorização específica para resistir às ações sísmicas. Para comparação, foi realizado o ensaio de um nó construído com armadura nervurada. Foi ainda realizado o ensaio cíclico de uma viga de betão armado recolhida de uma estrutura antiga. Foram elaborados modelos numéricos não-lineares para simular a resposta dos elementos ensaiados, concentrando especial atenção no mecanismo do escorregamento. Os resultados obtidos no âmbito desta tese contribuem para o avanço do conhecimento sobre o comportamento cíclico de elementos estruturais de betão armado com armadura lisa. As análises numéricas realizadas comprovam a necessidade de incluir os efeitos do escorregamento na modelação numérica deste tipo de estruturas de forma a representar com rigor a sua resposta às ações cíclicas.

Characterisation of the cyclic behaviour of reinforced concrete elements with plain bars

Sismos recentes comprovam a elevada vulnerabilidade dos edifícios existentes de betão armado. A resposta das estruturas aos sismos é fortemente condicionada pelas características da aderência aço-betão, que exibe degradação das propriedades iniciais quando sujeitas a carregamentos cíclicos e alternados. Este fenómeno é ainda mais gravoso para elementos com armadura lisa, predominantes na maioria das estruturas construídas até à década de 70 nos países do sul da Europa. A prática corrente de conceção, dimensionamento e pormenorização das estruturas antigas leva a que tenham características de comportamento e níveis de segurança associados não compatíveis com as exigências atuais. Os estudos realizados sobre o comportamento cíclico de elementos estruturais de betão armado com armadura lisa são ainda insuficientes para a completa caracterização deste tipo de elementos. Esta tese visou a caraterização da relação tensão de aderência versus escorregamento para elementos estruturais com armadura lisa e o estudo da resposta cíclica de pilares e nós viga-pilar de betão armado com armadura lisa. Foram realizados dez séries de ensaios de arrancamento (nove monotónicos e um cíclico) em provetes com varões lisos. Os resultados destes ensaios permitiram propor novas expressões empíricas para a estimativa dos parâmetros usados num modelo disponível na literatura para representação da relação tensão de aderência versus escorregamento. É ainda proposto um novo modelo monotónico para a relação tensão de aderência versus escorregamento que representa melhor a resposta após a resistência máxima de aderência. Uma campanha de ensaios unidirecionais em pilares e nós viga-pilar foi também realizada com o objetivo principal de caracterizar o comportamento cíclico deste tipo de elementos. No total foram realizados oito ensaios em pilares, sete ensaios em nós viga-pilar interiores e seis ensaios em nós viga-pilar exteriores representativos de estruturas antigas de betão armado com armadura lisa. Os resultados experimentais permitiram avaliar a influência do escorregamento e estudar o mecanismo de corte em nós e a evolução dos danos para elementos com armadura lisa. Com base nos resultados experimentais foi proposta uma adaptação na expressão do Eurocódigo 8-3 para o cálculo da capacidade última de rotação de elementos com armadura lisa. Foi também desenvolvido um estudo paramétrico, com diferentes estratégias de modelação não linear, para a simulação da resposta de pilares considerando o escorregamento da armadura lisa. Por último, foi proposto um novo modelo simplificado trilinear para o aço que contempla o efeito do escorregamento da armadura lisa.

Developmental Antecedents of Proactive and Reactive Rebelliousness: The Role of Parenting Style, Childhood Adversity, and Attachment

Adolescence is a time of developmental transition that for one in five young people is characterised by feelings of oppositionality, rebellion, and negativism. Despite the prevalent experience of teen turbulence and despite its significance within the phenomenological framework provided by reversal theory (RT), the childhood antecedents of rebelliousness in adolescence and adulthood have not been given extensive empirical attention within RT, although such work has been carried out using other constructs and theories. We examined recalled parenting style, childhood adversity, and attachment style in adulthood as correlates of proactive and reactive rebelliousness in a sample of 80 participants, aged 18 to 50 years. Each participant responded to a questionnaire package containing the revised Adult Attachment Scale, the Parental Bonding Instrument, the Childhood Experience of Care and Abuse Questionnaire, and the Negativism Dominance Scale. We found that paternal abusive parenting, followed by paternal parenting style, paternal neglect, and paternal antipathy were independently predictive of scores on proactive rebelliousness, the sensation-seeking form. Maternal and paternal indifferent parenting styles each were found to equivalently and independently predict scores on reactive rebelliousness, the interpersonal disaffection form. The results of this study suggest these two forms of rebelliousness may have distinctly different antecedents. A longitudinal study is needed to examine the potentially causal pathways that are suggested by the results of this cross-sectional research. We consider reversal theory explanations of these results and contrast them with complementary theoretical frameworks.