Oxygen isotope analysis of corals from the Gulf of California and the Gulf of Panama: application and implications for coral-based paleoclimate reconstructions [abstract]

EXTRACT (SEE PDF FOR FULL ABSTRACT): Coral-based reconstruction of past variability of sea surface conditions is improving our understanding of the tropical ocean-atmosphere system. We present oxygen isotope records from corals collected near the tip of Baja California (Baja) and the Gulf of Panama (Saboga).

A statistical index of growth condition in an aquaculture experiment

A simple statistical index, for evaluating the condition of growth in an aquaculture experiment and indicating the extent of effect of any plausible rival hypothesis, is presented.

Rhythmic stabilization of periodic orbits in a wedge

The paper addresses the rhythmic stabilization of periodic orbits in a wedge billiard with actuated edges. The output feedback strategy, based on the sole measurement of impact times, results from the combination of a stabilizing state feedback control law and a nonlinear deadbeat state estimator. It is shown that the robustness of both the control law and the observer leads to a simple rhythmic controller achieving a large basin of attraction. Copyright © 2005 IFAC.

Stabilization of periodic orbits in a wedge billiard

This paper introduces a stabilization problem for an elementary impact control system in the plane. The rich dynamical properties of the wedge billiard, combined to the relevance of the associated stabilization problem for feedback control issues in legged robotics make it a valuable benchmark for energy-based stabilization of impact control systems.

Age-dependence of urinary normal and modified nucleosides in childhood as determined by reversed-phase high-performance liquid chromatography

Modified nucleosides have been characterized as tumor markers for a number of malignant diseases. In order to use these markers in children, the age-dependence of the nucleoside levels in healthy children has to be established and taken into account in diagnostic decisions. In this study, the levels of 12 normal and modified nucleosides in urine of 166 healthy children and adolescents with an age between 1 day and 19 years are determined by reversed-phase HPLC, and age-dependent reference ranges are defined. The urinary nucleoside concentrations are related to the creatinine concentrations, which allows the use of randomly collected urine samples. All nucleoside levels in urine of children decrease with age, most pronounced during the first 4 years of life, and the age-dependence of the reference values of the individual nucleosides can be approximated by a mathematical function y = b(0) + b(1) (1/x) with the regression coefficients b(0) and b(1), the nucleoside levels y and the age x between 1 year and 19 years. In the very young children, the shifts in the nucleoside concentrations are more differentiated. Starting with low levels on the first day of life, the concentrations of all studied nucleosides rise up to an age of 1-2 months, when they reach their absolute maximum for all age periods, and then decrease. (C) 2004 Elsevier B.V. All rights reserved.

Orientational Harmonic Model for Rotation, Translation, and Scale Invariant Pattern Representation in Biological Vision

The proposed model, called the combinatorial and competitive spatio-temporal memory or CCSTM, provides an elegant solution to the general problem of having to store and recall spatio-temporal patterns in which states or sequences of states can recur in various contexts. For example, fig. 1 shows two state sequences that have a common subsequence, C and D. The CCSTM assumes that any state has a distributed representation as a collection of features. Each feature has an associated competitive module (CM) containing K cells. On any given occurrence of a particular feature, A, exactly one of the cells in CMA will be chosen to represent it. It is the particular set of cells active on the previous time step that determines which cells are chosen to represent instances of their associated features on the current time step. If we assume that typically S features are active in any state then any state has K^S different neural representations. This huge space of possible neural representations of any state is what underlies the model's ability to store and recall numerous context-sensitive state sequences. The purpose of this paper is simply to describe this mechanism.

VAMP - a vision based sensor network for health care hygiene

Adequate hand-washing has been shown to be a critical activity in preventing the transmission of infections such as MRSA in health-care environments. Hand-washing guidelines published by various health-care related institutions recommend a technique incorporating six hand-washing poses that ensure all areas of the hands are thoroughly cleaned. In this paper, an embedded wireless vision system (VAMP) capable of accurately monitoring hand-washing quality is presented. The VAMP system hardware consists of a low resolution CMOS image sensor and FPGA processor which are integrated with a microcontroller and ZigBee standard wireless transceiver to create a wireless sensor network (WSN) based vision system that can be retargeted at a variety of health care applications. The device captures and processes images locally in real-time, determines if hand-washing procedures have been correctly undertaken and then passes the resulting high-level data over a low-bandwidth wireless link. The paper outlines the hardware and software mechanisms of the VAMP system and illustrates that it offers an easy to integrate sensor solution to adequately monitor and improve hand hygiene quality. Future work to develop a miniaturized, low cost system capable of being integrated into everyday products is also discussed.

Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort

Background: Irritable bowel syndrome (IBS) is a common disorder that affects 10–15% of the population. Although characterised by a lack of reliable biological markers, the disease state is increasingly viewed as a disorder of the brain-gut axis. In particular, accumulating evidence points to the involvement of both the central and peripheral serotonergic systems in disease symptomatology. Furthermore, altered tryptophan metabolism and indoleamine 2,3-dioxygenase (IDO) activity are hallmarks of many stress-related disorders. The kynurenine pathway of tryptophan degradation may serve to link these findings to the low level immune activation recently described in IBS. In this study, we investigated tryptophan degradation in a male IBS cohort (n = 10) and control subjects (n = 26). Methods: Plasma samples were obtained from patients and healthy controls. Tryptophan and its metabolites were measured by high performance liquid chromatography (HPLC) and neopterin, a sensitive marker of immune activation, was measured using a commercially available ELISA assay. Results: Both kynurenine levels and the kynurenine:tryptophan ratio were significantly increased in the IBS cohort compared with healthy controls. Neopterin was also increased in the IBS subjects and the concentration of the neuroprotective metabolite kynurenic acid was decreased, as was the kynurenic acid:kynurenine ratio. Conclusion: These findings suggest that the activity of IDO, the immunoresponsive enzyme which is responsible for the degradation of tryptophan along this pathway, is enhanced in IBS patients relative to controls. This study provides novel evidence for an immune-mediated degradation of tryptophan in a male IBS population and identifies the kynurenine pathway as a potential source of biomarkers in this debilitating condition.

The role of the dopaminergic neurotrophin growth/differentiation factor-5 in the developing rat ventral midbrain

Growth differentiation factor-5 (GDF-5) is a member of the transforming growth factor-β superfamily, a family of proteins that play diverse roles in many aspects of cell growth, proliferation and differentiation. GDF-5 has also been shown to be a trophic factor for embryonic midbrain dopaminergic neurons in vitro (Krieglstein et al. 1995) and after transplantation to adult rats in vivo (Sullivan et al. 1998). GDF-5 has also been shown to have neuroprotective and neurorestorative effects on adult dopaminergic neurons in the substantia nigra in animal models of Parkinson’s disease (Sullivan et al. 1997, 1999; Hurley et al. 2004). This experimental evidence has lead to GDF-5 being proposed as a neurotrophic factor with potential for use in the treatment of Parkinson’s disease. However, it is not know if GDF-5 is expressed in the brain and whether it plays a role in dopaminergic neuron development. The experiments presented here aim to address these questions. To that end this thesis is divided into five separate studies each addressing a particular question associated with GDF-5 and its expression patterns and roles during the development of the rat midbrain. Expression of the GDF-5 in the developing rat ventral mesencephalon (VM) was found to begin at E12 and peak on E14, the day that dopaminergic neurons undergo terminal differentiation. In the adult rat, GDF-5 was found to be restricted to heart and brain, being expressed in many areas of the brain, including striatum and midbrain. This indicated a role for GDF-5 in the development and maintenance of dopaminergic neurons. The appropriate receptors for GDF-5 (BMPR-II and BMPR-Ib) were found to be expressed at high levels in the rat VM at E14 and BMPR-II expression was demonstrated on dopaminergic neurons in the E13 mouse VM. GDF-5 resulted in a three-fold increase in the numbers of dopaminergic neurons in cultures of E14 rat VM, without affecting the numbers of neurones or total cells. GDF-5 was found to increase the proportion of neurons that were dopaminergic. The numbers of Nurr1-positive cells were not affected by GDF-5 treatment, but GDF-5 did increase the numbers of Nurr1- positive cells that expressed tyrosine hydroxylase (TH). Taken together this data indicated that GDF-5 increases the conversion of Nurr1-positive, TH-negative cells to Nurr1-positive, TH-positive cells. In GDF-5 treated cultures, total neurite length, neurite arborisation and somal area of dopaminergic were all significantly increased compared to control cultures. Thus this study showed that GDF-5 increased the numbers and morphological differentiation of VM dopaminergic neurones in vitro. In order to examine if GDF-5 could induce a dopaminergic phenotype in neural progenitor cells, neurosphere cultures prepared from embryonic rat VM were established. The effect of the gestational age of the donor VM on the proportion of cell types generated from neurospheres from E12, E13 and E14 VM was examined. Dopaminergic neurons could only be generated from neurospheres which were prepared from E12 VM. Thus in subsequent studies the effect of GDF-5 on dopaminergic induction was examined in progentior cell cultures prepared from the E12 rat VM. In primary cultures of E12 rat VM, GDF-5 increased the numbers of TH-positive cells without affecting the proliferation or survival of these cells. In cultures of expanded neural progenitor cells from the E12 rat VM, GDF-5 increased the expression of Nurr1 and TH, an action that was dependent on signalling through the BMPR-Ib receptor. Taken together, these experiments provide evidence that GDF-5 is expressed in the developing rat VM, is involved in both the induction of a dopaminergic phenotype in cells of the VM and in the subsequent morphological development of these dopaminergic neurons

Paracetamol metabolism in postoperative patients

Introduction: Despite being available for more than 50 years, there is still much to learn about paracetamol. Postoperative analgesic regimens that maintain good pain control while minimising exposure to opiates are beneficial and paracetamol has had a resurgence in this role since an IV formulation came to market. However there is evidence to suggest currently licensed doses are sub-therapeutic, especially when administered orally or rectally. Higher, unlicensed doses are now being advocated but, prior to this study, there was little evidence of their safety in surgical patients. When assessing drug safety in surgical patients a number of surgery and patient related factors influence results, and these must be considered. Methods: Major and intermediate surgical patients were recruited from two hospitals in Ireland. They were administered IV paracetamol at either 9g or 4g daily doses. In addition they received daily sub therapeutic doses of four other medicines to indicate the activity of their CYP450 enzymes that are involved in paracetamol metabolism. Urine and blood samples were collected to determine paracetamol pharmacokinetics, CYP450 activity, inflammatory cytokine concentration and for evidence of hepatotoxicity. Results: There were 33 patients that participated in the study. There was no evidence of clinically significant hepatotoxicity occurring in any patient during the study period, but there could have been changes following this time. Paracetamol disposition was shown to change, however half-life remained relatively constant. There were a number of changes to the way paracetamol was metabolised following surgery that maintained this rate of elimination. Conclusion: Doses of up to 9g per day given to major surgical patients for up to five days postoperatively produced no evidence of hepatotoxicity. Further research is warranted to determine the clinical utility of these higher doses

Work experience in transition year: a mixed methods study of subject and career choices

Transition Year (TY) has been a feature of the Irish Education landscape for 39 years. Work experience (WE) has become a key component of TY. WE is defined as a module of between five and fifteen days duration where students engage in a work placement in the broader community. It places a major emphasis on building relationships between schools and their external communities and concomitantly between students and their potential future employers. Yet, the idea that participation in a TY work experience programme could facilitate an increased awareness of potential careers has drawn little attention from the research community. This research examines the influence WE has on the subsequent subjects choices made by students along with the effects of that experience on the students’ identities and emerging vocational identities. Socio-cultural Learning Theory and Occupational Choice Theory frame the overall study. A mixed methods approach to data collection was adopted through the administration of 323 quantitative questionnaires and 32 individual semi-structured interviews in three secondary schools. The analysis of the data was conducted using a grounded theory approach. The findings from the research show that WE makes a significant contribution to the students’ sense of agency in their own lives. It facilitates the otherwise complex process of subject choice, motivates students to work harder in their senior cycle, introduces them to the concepts of active, experience-based and self-directed learning, while boosting their self-confidence and nurturing the emergence of their personal and vocational identities. This research is a gateway to further study in this field. It also has wide reaching implications for students, teachers, school authorities, parents and policy makers regarding teaching and learning in our schools and the value of learning beyond the walls of the classroom.

Expression and function of the neurotrophic factors GDF5 and GDNF in the nigrostriatal system during development and in rat models of Parkinson's disease

Growth/differentiation factor 5 (GDF5) and glial cell line-derived neurotrophic factor (GDNF) are neurotrophic factors that promote the survival of midbrain dopaminergic neurons in vitro and in vivo. Both factors have potent neurotrophic and neuroprotective effects in rat models of Parkinson's disease (PD), and may represent promising new therapies for PD. The aim of the present study was to investigate the endogenous expression and function of GDF5 and GDNF in the nigrostriatal dopaminergic system during development and in rat models of PD. Examination of the temporal expression patterns of endogenous GDF5, GDNF, and their respective receptors, in the developing and adult nigrostriatal dopaminergic system suggest that these factors play important roles in promoting the survival and maturation of midbrain dopaminergic neurons during the period of postnatal programmed cell death. The relative levels of GDF5 and GDNF mRNAs in the midbrain and striatum, and their individual temporal expression patterns during development, suggest that their modes of actions are quite distinct in vivo. Furthermore, the sustained expression of GDF5, GDNF, and their receptors into adulthood suggest roles for these factors in the continued support and maintenance of mature nigrostriatal dopaminergic neurons. The present study found that endogenous GDF5, GDNF, and their receptors are differentially expressed in two 6-hydroxydopamine-induced lesion adult rat models of PD. In both terminal and axonal lesion models of PD, GDF5 mRNA levels in the striatum increased at 10 days post-lesion, while GDNF mRNA levels in the nigrostriatal system decreased at 10 and 28 days post-lesion. Thus, despite the fact that exogenous GDF5 and GDNF have similar effects on midbrain dopaminergic neurons in vitro and in vivo, their endogenous responses to a neurotoxic injury are quite distinct. These results highlight the importance of studying the temporal dynamic changes in neurotrophic factor expression during development and in animal models of PD.