Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury.

BACKGROUND: Rat oligonucleotide microarrays were used to detect changes in gene expression in the dorsal root ganglion (DRG) 3 days following sciatic nerve transection (axotomy). Two comparisons were made using two sets of triplicate microarrays, naïve versus naïve and naïve versus axotomy. RESULTS: Microarray variability was assessed using the naïve versus naïve comparison. These results support use of a P < 0.05 significance threshold for detecting regulated genes, despite the large number of hypothesis tests required. For the naïve versus axotomy comparison, a 2-fold cut off alone led to an estimated error rate of 16%; combining a >1.5-fold expression change and P < 0.05 significance reduced the estimated error to 5%. The 2-fold cut off identified 178 genes while the combined >1.5-fold and P < 0.05 criteria generated 240 putatively regulated genes, which we have listed. Many of these have not been described as regulated in the DRG by axotomy. Northern blot, quantitative slot blots and in situ hybridization verified the expression of 24 transcripts. These data showed an 83% concordance rate with the arrays; most mismatches represent genes with low expression levels reflecting limits of array sensitivity. A significant correlation was found between actual mRNA differences and relative changes between microarrays (r(2 )= 0.8567). Temporal patterns of individual genes regulation varied. CONCLUSIONS: We identify parameters for microarray analysis which reduce error while identifying many putatively regulated genes. Functional classification of these genes suggest reorganization of cell structural components, activation of genes expressed by immune and inflammatory cells and down-regulation of genes involved in neurotransmission

GDNF selectively promotes regeneration of injury-primed sensory neurons in the lesioned spinal cord

Axonal regeneration within the CNS fails due to the growth-inhibitory environment and the limited intrinsic growth capacity of injured neurons. Injury to DRG peripheral axons induces expression of growth associated genes including members of the glial-derived neurotrophic factor (GDNF) signaling pathway and “pre-conditions” the injured cells into an active growth state, enhancing growth of their centrally projecting axons. Here, we show that pre-conditioning DRG neurons prior to culturing increased neurite outgrowth, which was further enhanced by GDNF in a bell-shaped growth response curve. In vivo, GDNF delivered directly to DRG cell bodies facilitated the pre-conditioning effect, further enhancing axonal regeneration beyond spinal cord lesions. Consistent with the in vitro results, the in vivo effect was seen only at low GDNF concentrations. We conclude that peripheral nerve injury upregulates GDNF signaling pathway components and that exogenous GDNF treatment selectively promotes axonal growth of injury-primed sensory neurons in a concentration-dependent fashion

The effect of phosphate, fluorine, and soda content of the glass on the mechanical properties of the glass ionomer (polyalkenoate) cements

The authors would like to thank the Department of Trade and Industry, UK, under the project number of TP/5/REG/6/I/H0669A

Water Banks: What Have We Learnt from the International Experience?

In recent decades, the use of economic instruments has been promoted as a way to improve water demand management, required due to the difficulty of further supply increases. Against this backdrop, this paper analyses the potential of water banks as a type of water market that can provide institutional flexibility in the allocation of water resources among different users. Research has involved an extensive review of the literature, which has allowed us to identify different types of water banks that operate around the world, as well as an analysis of the experiences of water banks implemented to date, in order to assess the performance of this economic instrument in improving water management. This has provided evidence that water banks, if properly implemented, can be a useful tool for improving governance of water resources. Finally, the analysis has enabled us to propose a number of guidelines on how to improve the implementation of water banks in different countries around the worl

ADARRI:a novel method to detect spurious R-peaks in the electrocardiogram for heart rate variability analysis in the intensive care unit

We developed a simple and fully automated method for detecting artifacts in the R-R interval (RRI) time series of the ECG that is tailored to the intensive care unit (ICU) setting. From ECG recordings of 50 adult ICU-subjects we selected 60 epochs with valid R-peak detections and 60 epochs containing artifacts leading to missed or false positive R-peak detections. Next, we calculated the absolute value of the difference between two adjacent RRIs (adRRI), and obtained the empirical probability distributions of adRRI values for valid R-peaks and artifacts. From these, we calculated an optimal threshold for separating adRRI values arising from artifact versus non-artefactual data. We compared the performance of our method with the methods of Berntson and Clifford on the same data. We identified 257,458 R-peak detections, of which 235,644 (91.5%) were true detections and 21,814 (8.5%) arose from artifacts. Our method showed superior performance for detecting artifacts with sensitivity 100%, specificity 99%, precision 99%, positive likelihood ratio of 100 and negative likelihood ratio <0.001 compared to Berntson’s and Clifford’s method with a sensitivity, specificity, precision and positive and negative likelihood ratio of 99%, 78%, 82%, 4.5, 0.013 for Berntson’s method and 55%, 98%, 96%, 27.5, 0.460 for Clifford’s method, respectively. A novel algorithm using a patient-independent threshold derived from the distribution of adRRI values in ICU ECG data identifies artifacts accurately, and outperforms two other methods in common use. Furthermore, the threshold was calculated based on real data from critically ill patients and the algorithm is easy to implement

Area selection for diamonds using magnetotellurics : examples from southern Africa

Author Posting. © Elsevier B.V., 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Lithos 112 (2009): 83-92, doi:10.1016/j.lithos.2009.06.011.Southern Africa, particularly the Kaapvaal Craton, is one of the world’s best natural laboratories for studying the lithospheric mantle given the wealth of xenolith and seismic data that exist for it. The Southern African Magnetotelluric Experiment (SAMTEX) was launched to complement these databases and provide further constraints on physical parameters and conditions by obtaining information about electrical conductivity variations laterally and with depth. Initially it was planned to acquire magnetotelluric data on profiles spatially coincident with the Kaapvaal Seismic Experiment, however with the addition of seven more partners to the original four through the course of the experiment, SAMTEX was enlarged from two to four phases of acquisition, and extended to cover much of Botswana and Namibia. The complete SAMTEX dataset now comprises MT data from over 675 distinct locations in an area of over one million square kilometres, making SAMTEX the largest regional-scale MT experiment conducted to date. Preliminary images of electrical resistivity and electrical resistivity anisotropy at 100 km and 200 km, constructed through approximate one-dimensional methods, map resistive regions spatially correlated with the Kaapvaal, Zimbabwe and Angola Cratons, and more conductive regions spatially associated with the neighbouring mobile belts and the Rehoboth Terrain. Known diamondiferous kimberlites occur primarily on the boundaries between the resistive or isotropic regions and conductive or anisotropic regions. Comparisons between the resistivity image maps and seismic velocities from models constructed through surface wave and body wave tomography show spatial correlations between high velocity regions that are resistive, and low velocity regions that are conductive. In particular, the electrical resistivity of the sub-continental lithospheric mantle of the Kaapvaal Craton is determined by its bulk parameters, so is controlled by a bulk matrix property, namely temperature, and to a lesser degree by iron content and composition, and is not controlled by contributions from interconnected conducting minor phases, such as graphite, sulphides, iron oxides, hydrous minerals, etc. This makes quantitative correlations between velocity and resistivity valid, and a robust regression between the two gives an approximate relationship of Vs [m/s] = 0.045*log(resistivity [ohm.m]).We especially thank our academic funding sponsors; the Continental Dynamics programme of the U.S. National Science Foundation, the South African Department of Science and Technology, and Science Foundation Ireland

Opinion dynamics: models, extensions and external effects

Recently, social phenomena have received a lot of attention not only from social scientists, but also from physicists, mathematicians and computer scientists, in the emerging interdisciplinary field of complex system science. Opinion dynamics is one of the processes studied, since opinions are the drivers of human behaviour, and play a crucial role in many global challenges that our complex world and societies are facing: global financial crises, global pandemics, growth of cities, urbanisation and migration patterns, and last but not least important, climate change and environmental sustainability and protection. Opinion formation is a complex process affected by the interplay of different elements, including the individual predisposition, the influence of positive and negative peer interaction (social networks playing a crucial role in this respect), the information each individual is exposed to, and many others. Several models inspired from those in use in physics have been developed to encompass many of these elements, and to allow for the identification of the mechanisms involved in the opinion formation process and the understanding of their role, with the practical aim of simulating opinion formation and spreading under various conditions. These modelling schemes range from binary simple models such as the voter model, to multi-dimensional continuous approaches. Here, we provide a review of recent methods, focusing on models employing both peer interaction and external information, and emphasising the role that less studied mechanisms, such as disagreement, has in driving the opinion dynamics. [...]Comment: 42 pages, 6 figure

A Randomized Trial Evaluating Prosaptide™ for HIV-Associated Sensory Neuropathies: Use of an Electronic Diary to Record Neuropathic Pain

Objectives: To examine the efficacy and safety of Prosaptide™ (PRO) for the treatment of painful HIV-associated sensory neuropathies (HIV-SN). Design: A randomized, double-blind, placebo-controlled, multicenter study in participants with sensory neuropathy. Pain modulating therapy was discontinued prior to baseline. Participants were stratified by sural sensory nerve action potential (SNAP) amplitude. Participants were trained to use an electronic diary (ED) to record pain. Setting: Peripheral neuropathies are common complications of HIV infection. The pathogenesis is unknown and currently treatments are restricted to symptomatic measures. We examined PRO against placebo (PBO) for treatment of painful HIV-SN and performed a post-hoc evaluation of an electronic diary (ED) to record HIV-associated neuropathic pain. Participants: Eligible participants included adults with neurologist-confirmed painful HIV-SN.Interventions 2, 4, 8, or 16 mg/d PRO or PBO administered via subcutaneous (SC) injection for six weeks. Neurotoxic antiretroviral drug usage was held constant.Outcome Measures Changes from baseline in the weekly average of evaluable daily random prompts measuring pain using the Gracely pain scale and adverse events. Results: 237 participants were randomized. The study was stopped after a planned futility analysis. There were no between-group differences in the frequency of adverse events or laboratory toxicities. The 6-week mean (sd) Gracely pain scale changes were −0.12 (0.23), −0.24 (0.35), −0.15 (0.32), −0.18 (0.34), and −0.18 (0.32) for the 2, 4, 8, 16 mg, and PBO arms respectively. A similar variability of pain changes recorded using the ED were noted compared to previous trials that used paper collection methods.Conclusions 6-week treatment with PRO was safe but not effective at reducing HIV-associated neuropathic pain. Use of an ED to record neuropathic pain is novel in HIV-SN, resulted in reasonable compliance in recording pain data, but did not decrease the variability of pain scores compared to historical paper collection methods. Trial Registration: Current Controlled Trials NCT0028637

Exploring community nurses' perceptions of life review in palliative care

Aims and objectives. This exploratory study aimed to identify community nurses’ understanding of life review as a therapeutic intervention for younger people requiring palliative care. The objectives set out to: (i) Describe the participants’ understanding of reminiscence and life review (ii) Detail their current ideas regarding a structured approach to using life review in the community setting. (iii) Outline their understanding of the possible advantages and limitations of life review in relation to palliative care. (iv) Identify future training requirements. Background. The literature review illustrated how the eighth developmental stage of Erikson's theory, ego-integrity vs. despair, is a ‘crisis’ often faced by older people entering the final stage of life. Life review is considered a useful therapeutic intervention in the resolution of this crisis. Younger terminally ill people in the palliative stage of an illness may face the same final crises due to their reduced lifespan. Therefore, this study explored the benefits and limitations of life review as an intervention in palliative care. Method. The study used a purposive sample of community nurses responsible for delivering generic and specialist palliative care. A qualitative method of data collection in the form of three focus group interviews was used. Subsequent data were manually analysed, categorized and coded with associations between the themes identified. Results. The findings suggested that community nurses have limited knowledge pertaining to the use of life review and tend to confuse the intervention with reminiscence. Furthermore, they believed that life review could potentially cause harm to practitioners engaged in listening to another person's life story. However, the participants concur that with appropriate training they would find life review a useful intervention to use in palliative care. Conclusions. The results led to the identification of a number of key recommendations: Community nurses require specific education in the technicalities of life review and additional interpersonal skills training. The need for formalized support through clinical supervision is also recognized and discussed. Finally, suggestions are offered regarding the need to generate wider evidence and how, possibly, to integrate life review into existing palliative care services. Relevance to clinical practice. This study has demonstrated that community nurses are keen to extend the support offered to younger terminally ill people who are in the palliative stage of their illness. Despite having limited knowledge of life the main components and underpinning theory pertaining to life review participants could appreciate the potential of life review as a therapeutic intervention in palliative care and were keen to learn more about its use and gain the necessary knowledge and skill