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Showing papers by "University of Newcastle published in 2007"


01 Jan 2007
TL;DR: In this paper, the main definitions relating to dependability, a generic concept including a special case of such attributes as reliability, availability, safety, integrity, maintainability, etc.
Abstract: This paper gives the main definitions relating to dependability, a generic concept including a special case of such attributes as reliability, availability, safety, integrity, maintainability, etc. Security brings in concerns for confidentiality, in addition to availability and integrity. Basic definitions are given first. They are then commented upon, and supplemented by additional definitions, which address the threats to dependability and security (faults, errors, failures), their attributes, and the means for their achievement (fault prevention, fault tolerance, fault removal, fault forecasting). The aim is to explicate a set of general concepts, of relevance across a wide range of situations and, therefore, helping communication and cooperation among a number of scientific and technical communities, including ones that are concentrating on particular types of system, of system failures, or of causes of system failures.

4,335 citations


Journal ArticleDOI
TL;DR: It is concluded that post‐copulatory mechanisms provide a more reliable way of selecting a genetically compatible mate than pre-copulatory mate choice and that some of the best evidence for cryptic female choice by sperm selection is due to selection of more compatible sperm.
Abstract: The aim of this review is to consider the potential benefits that females may gain from mating more than once in a single reproductive cycle. The relationship between non-genetic and genetic benefits is briefly explored. We suggest that multiple mating for purely non-genetic benefits is unlikely as it invariably leads to the possibility of genetic benefits as well. We begin by briefly reviewing the main models for genetic benefits to mate choice, and the supporting evidence that choice can increase offspring performance and the sexual attractiveness of sons. We then explain how multiple mating can elevate offspring fitness by increasing the number of potential sires that compete, when this occurs in conjunction with mechanisms of paternity biasing that function in copula or post-copulation. We begin by identifying cases where females use pre-copulatory cues to identify mates prior to remating. In the simplest case, females remate because they identify a superior mate and 'trade up' genetically. The main evidence for this process comes from extra-pair copulation in birds. Second, we note other cases where pre-copulatory cues may be less reliable and females mate with several males to promote post-copulatory mechanisms that bias paternity. Although a distinction is drawn between sperm competition and cryptic female choice, we point out that the genetic benefits to polyandry in terms of producing more viable or sexually attractive offspring do not depend on the exact mechanism that leads to biased paternity. Post-copulatory mechanisms of paternity biasing may: (1) reduce genetic incompatibility between male and female genetic contributions to offspring; (2) increase offspring viability if there is a positive correlation between traits favoured post-copulation and those that improve performance under natural selection; (3) increase the ability of sons to gain paternity when they mate with polyandrous females. A third possibility is that genetic diversity among offspring is directly favoured. This can be due to bet-hedging (due to mate assessment errors or temporal fluctuations in the environment), beneficial interactions between less related siblings or the opportunity to preferentially fertilise eggs with sperm of a specific genotype drawn from a range of stored sperm depending on prevailing environmental conditions. We use case studies from the social insects to provide some concrete examples of the role of genetic diversity among progeny in elevating fitness. We conclude that post-copulatory mechanisms provide a more reliable way of selecting a genetically compatible mate than pre-copulatory mate choice. Some of the best evidence for cryptic female choice by sperm selection is due to selection of more compatible sperm. Two future areas of research seem likely to be profitable. First, more experimental evidence is needed demonstrating that multiple mating increases offspring fitness via genetic gains. Second, the role of multiple mating in promoting assortative fertilization and increasing reproductive isolation between populations may help us to understand sympatric speciation.

1,778 citations


Journal ArticleDOI
06 Jul 2007-Science
TL;DR: It is proposed that estrogen-mediated inhibition of IL-6 production by KCs reduces liver cancer risk in females, and these findings may be used to prevent HCC in males.
Abstract: Hepatocellular carcinoma (HCC), the most common liver cancer, occurs mainly in men. Similar gender disparity is seen in mice given a chemical carcinogen, diethylnitrosamine (DEN). DEN administration caused greater increases in serum interleukin-6 (IL-6) concentration in males than it did in females. Furthermore, ablation of IL-6 abolished the gender differences in hepatocarcinogenesis in mice. DEN exposure promoted production of IL-6 in Kupffer cells (KCs) in a manner dependent on the Toll-like receptor adaptor protein MyD88, ablation of which also protected male mice from DEN-induced hepatocarcinogenesis. Estrogen inhibited secretion of IL-6 from KCs exposed to necrotic hepatocytes and reduced circulating concentrations of IL-6 in DEN-treated male mice. We propose that estrogen-mediated inhibition of IL-6 production by KCs reduces liver cancer risk in females, and these findings may be used to prevent HCC in males.

1,712 citations


Journal ArticleDOI
TL;DR: This paper presents an overview of nanopositioning technologies and devices emphasizing the key role of advanced control techniques in improving precision, accuracy, and speed of operation of these systems.
Abstract: Nanotechnology is the science of understanding matter and the control of matter at dimensions of 100 nm or less. Encompassing nanoscale science, engineering, and technology, nanotechnology involves imaging, measuring, modeling, and manipulation of matter at this level of precision. An important aspect of research in nanotechnology involves precision control and manipulation of devices and materials at a nanoscale, i.e., nanopositioning. Nanopositioners are precision mechatronic systems designed to move objects over a small range with a resolution down to a fraction of an atomic diameter. The desired attributes of a nanopositioner are extremely high resolution, accuracy, stability, and fast response. The key to successful nanopositioning is accurate position sensing and feedback control of the motion. This paper presents an overview of nanopositioning technologies and devices emphasizing the key role of advanced control techniques in improving precision, accuracy, and speed of operation of these systems.

1,027 citations


Journal ArticleDOI
TL;DR: In the steadily expanding field of fluorescent dyes, labels and electroluminescent materials difluoroboron-dipyrromethenes play a prominent role.
Abstract: In the steadily expanding field of fluorescent dyes, labels and electroluminescent materials difluoroboron-dipyrromethenes play a prominent role The review highlights recent advances made with these boron-stabilized cyanine dyes The chemistry at the boron atom and increase of delocalization on the organic core allows one to address the problems of Stokes’ shifts, colours and emission wavelengths spanning from green to the NIR The outcome is a diversity of molecules prepared by different strategies and exhibiting interesting and tunable spectroscopic, electrochemical and chemical properties This perspective article describes the scope and spectroscopic attributes of this new class of fluorescent dyes amenable to applications in various disciplines

839 citations



Journal ArticleDOI
TL;DR: Valproate is better tolerated than topiramate and more efficacious than lamotrigine, and should remain the drug of first choice for many patients with generalised and unclassified epilepsies, and because of known potential adverse effects of valproate during pregnancy, the benefits for seizure control in women of childbearing years should be considered.

774 citations


Journal ArticleDOI
TL;DR: In Westernized societies, average consumption of n-6 polyunsaturated fatty acids (PUFAs) far exceeds nutritional requirements, and adequate powered trials are required to determine the extent to which this aspect of the authors' diets does influence their fertility.
Abstract: In Westernized societies, average consumption of n-6 polyunsaturated fatty acids (PUFAs) far exceeds nutritional requirements. The ratio of n-6 to n-3 PUFAs is generally >10:1 whereas on a primitive human diet it was closer to 1:1. Diets fed to intensively farmed livestock have followed a similar trend. Both n-6 and n-3 PUFAs can influence reproductive processes through a variety of mechanisms. They provide the precursors for prostaglandin synthesis and can modulate the expression patterns of many key enzymes involved in both prostaglandin and steroid metabolism. They are essential components of all cell membranes. The proportions of different PUFAs in tissues of the reproductive tract reflect dietary consumption. PUFA supplements (particularly n-3 PUFAs in fish oil) are promoted for general health reasons. Fish oils may also benefit fertility in cattle and reduce the risk of preterm labor in women, but in both cases current evidence to support this is inconclusive. Gamma-linolenic acid containing oils can alter the types of prostaglandins produced by cells in vitro, but published data to support claims relating to effects on reproductive health are lacking. Spermatozoa require a high PUFA content to provide the plasma membrane with the fluidity essential at fertilization. However, this makes spermatozoa particularly vulnerable to attack by reactive oxygen species, and lifestyle factors promoting oxidative stress have clear associations with reduced fertility. Adequately powered trials that control for the ratios of different PUFAs consumed are required to determine the extent to which this aspect of our diets does influence our fertility.

668 citations


Journal ArticleDOI
TL;DR: It is proposed that mitochondrial ROS is a major determinant of telomere-dependent senescence at the single-cell level that is responsible for cell-to-cell variation in replicative lifespan.
Abstract: Aging is an inherently stochastic process, and its hallmark is heterogeneity between organisms, cell types, and clonal populations, even in identical environments. The replicative lifespan of primary human cells is telomere dependent; however, its heterogeneity is not understood. We show that mitochondrial superoxide production increases with replicative age in human fibroblasts despite an adaptive UCP-2–dependent mitochondrial uncoupling. This mitochondrial dysfunction is accompanied by compromised [Ca2+]i homeostasis and other indicators of a retrograde response in senescent cells. Replicative senescence of human fibroblasts is delayed by mild mitochondrial uncoupling. Uncoupling reduces mitochondrial superoxide generation, slows down telomere shortening, and delays formation of telomeric γ-H2A.X foci. This indicates mitochondrial production of reactive oxygen species (ROS) as one of the causes of replicative senescence. By sorting early senescent (SES) cells from young proliferating fibroblast cultures, we show that SES cells have higher ROS levels, dysfunctional mitochondria, shorter telomeres, and telomeric γ-H2A.X foci. We propose that mitochondrial ROS is a major determinant of telomere-dependent senescence at the single-cell level that is responsible for cell-to-cell variation in replicative lifespan.

633 citations


Journal ArticleDOI
TL;DR: This paper will focus on two contexts where collaborative research teams have found solastalgia to be evident: the experiences of persistent drought in rural NSW and the impact of large-scale open-cut coal mining on individuals in the Upper Hunter Valley of NSW.
Abstract: Objective: Solastalgia is a new concept developed to give greater meaning and clarity to environmentally induced distress. As opposed to nostalgia – the melancholia or homesickness experienced by i...

631 citations


Journal ArticleDOI
01 Jan 2007
TL;DR: A review of the technologies for coal-based power generation closest to commercial application involving carbon capture is presented in this paper, where the R&D challenges identified for the combustion scientist and engineer are those of design, optimisation and operational aspects of new combustion and gasification plant, controlling the gas quality required by CCS related units and associated emission compliance, and gas separations.
Abstract: A review of the technologies for coal-based power generation closest to commercial application involving carbon capture is presented. Carbon capture and storage (CCS) developments are primarily adaptations of conventional combustion systems, with additional unit operations such as bulk oxygen supply, CO2 capture by sorbents, CO2 compression, and storage. They use pulverized coal combustion in entrained flow—the dominant current technology for coal-based power, or gasification in entrained flow, although similar concepts apply to other solid–gas contacting systems such as fluidized beds. Currently, the technologies have similar generation efficiencies and are associated with efficiency penalties and electricity cost increases due to operations required for carbon capture. The R&D challenges identified for the combustion scientist and engineer, with current understanding being detailed, are those of design, optimisation and operational aspects of new combustion and gasification plant, controlling the gas quality required by CCS related units and associated emission compliance, and gas separations. Fundamental research needs include fuel reactions at pressure, and in O2/CO2 atmospheres, as few studies have been made in this area. Laboratory results interpreted and then included in CFD models of combustion operations are necessary. Also identified, but not detailed, are combustion issues in gas turbines for IGCC and IGCC-CCS. Fundamental studies should be a component of pilot-plant and demonstrations at practical scale being planned. Concepts for new designs of combustion equipment are also necessary for the next generation of technologies. The challenges involved with the design and operation of these integrated systems, while supplying electricity on demand, are considerable.

Journal ArticleDOI
TL;DR: Treated with glucose-potassium-insulin GKI infusions to maintain euglycaemia immediately after the acute event reduces death at 90 days, although the study was underpowered and alternative results cannot be excluded.
Abstract: Summary Background Hyperglycaemia after acute stroke is a common finding that has been associated with an increased risk of death. We sought to determine whether treatment with glucose-potassium-insulin (GKI) infusions to maintain euglycaemia immediately after the acute event reduces death at 90 days. Methods Patients presenting within 24 h of stroke onset and with admission plasma glucose concentration between 6·0–17·0 mmol/L were randomly assigned to receive variable-dose-insulin GKI (intervention) or saline (control) as a continuous intravenous infusion for 24 h. The purpose of GKI infusion was to maintain capillary glucose at 4–7 mmol/L, with no glucose intervention in the control group. The primary outcome was death at 90 days, and the secondary endpoint was avoidance of death or severe disability at 90 days. Additional planned analyses were done to determine any differences in residual disability or neurological and functional recovery. The trial was powered to detect a mortality difference of 6% (sample size 2355), with 83% power, at the 5% two-sided significance level. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN 31118803) Findings The trial was stopped due to slow enrolment after 933 patients were recruited. For the intention-to-treat data, there was no significant reduction in mortality at 90 days (GKI vs control: odds ratio 1·14, 95% CI 0·86–1·51, p=0·37). There were no significant differences for secondary outcomes. In the GKI group, overall mean plasma glucose and mean systolic blood pressure were significantly lower than in the control group (mean difference in glucose 0·57 mmol/L, p Interpretation GKI infusions significantly reduced plasma glucose concentrations and blood pressure. Treatment within the trial protocol was not associated with significant clinical benefit, although the study was underpowered and alternative results cannot be excluded.

Journal ArticleDOI
TL;DR: It seems that parent training can successfully contribute to intervention for young children with ASD, however, the review highlights the need for improved research in this area.
Abstract: Background Recent estimates concerning the prevalence of autism spectrum disorder (ASD) suggest that at least one in 200 children is affected. This group of children and families have important service needs. The involvement of parents in implementing intervention strategies designed to help their autistic children has long been accepted as helpful. The potential benefits are increased skills and reduced stress for parents as well as children. Methods This research review focused on interventions for children aged 1‐6 years, and was carried out using systematic methodology: a comprehensive search of psychological, educational and biomedical databases, as well as bibliographies and reference lists of key articles, contact with experts in the field, and hand search of key journals. Only studies which involved a concurrent element of control were included. Results The review found very few studies that had adequate research design from which to draw conclusions about the effectiveness of parent-implemented early intervention. Both randomized and controlled studies tended to suggest that parent training leads to improved child communicative behaviour, increased maternal knowledge of autism, enhanced maternal communication style and parent child interaction, and reduced maternal depression. Conclusion It seems that parent training can successfully contribute to intervention for young children with ASD. However, the review highlights the need for improved research in this area.

Journal ArticleDOI
TL;DR: A representation space is introduced, to be called the complexity-entropy causality plane, which contains suitable functionals of the pertinent probability distribution, namely, the entropy of the system and an appropriate statistical complexity measure, respectively.
Abstract: Chaotic systems share with stochastic processes several properties that make them almost undistinguishable. In this communication we introduce a representation space, to be called the complexity-entropy causality plane. Its horizontal and vertical axis are suitable functionals of the pertinent probability distribution, namely, the entropy of the system and an appropriate statistical complexity measure, respectively. These two functionals are evaluated using the Bandt-Pompe recipe to assign a probability distribution function to the time series generated by the system. Several well-known model-generated time series, usually regarded as being of either stochastic or chaotic nature, are analyzed so as to illustrate the approach. The main achievement of this communication is the possibility of clearly distinguishing between them in our representation space, something that is rather difficult otherwise.

Journal ArticleDOI
15 Feb 2007-Neuron
TL;DR: The effects of insufficient recruitment of fast-spiking cells at the network and behavioral level are shown and the role of this subpopulation for working and episodic-like memory is demonstrated.

Journal ArticleDOI
TL;DR: In this paper, an interpretational framework for the analysis of a diverse set of geological structures that breach sealing sequences and allow fluids to flow vertically or subvertically across the seal.
Abstract: We present an interpretational framework for the analysis of a diverse set of geological structures that breach sealing sequences and allow fluids to flow vertically or subvertically across the seal. In so doing, they act as seal bypass systems (SBS). We define SBS as seismically resolvable geological features embedded within sealing sequences that promote cross-stratal fluid migration and allow fluids to bypass the pore network. If such bypass systems exist within a given seal sequence, then predictions of sealing capacity based exclusively on the flow properties (capillary entry pressure and hydraulic conductivity) of the bulk rock can potentially be negated by the capacity of the bypass system to breach the grain and pore network. We present a range of examples of SBS affecting contrasting types of sealing sequences using three-dimensional (3-D) seismic data. These examples show direct evidence of highly focused vertical or subvertical fluid flow from subsurface reservoirs up through the seal sequence, with leakage internally at higher levels or to the surface as seeps.We classify SBS into three main groups based on seismic interpretational criteria: (1) fault related, (2) intrusion related, and (3) pipe related. We show how each group exhibits different modes of behavior with different scaling relationships between flux and dimensions and different short- and long-term impacts on seal behavior.

Journal ArticleDOI
TL;DR: This review summarizes recent debates and considers the pragmatic and economic issues associated with evaluating whole-population interventions while maintaining scientific validity and credibility.

Journal ArticleDOI
TL;DR: It is concluded that a broadly conceptualized cognitive behavioural model of MUS suggests a novel and plausible mechanism of symptom generation and has heuristic value.

Journal ArticleDOI
TL;DR: SCH treated by L-thyroxine leads to a significant improvement in CV risk factors and symptoms of tiredness, and the CV risk factor reduction is related to the increased level of achieved free T(4) concentration.
Abstract: Context: Subclinical hypothyroidism (SCH) is defined as raised serum TSH levels with circulating thyroid hormones within the reference range. It is uncertain whether treatment of SCH with l-thyroxine improves cardiovascular (CV) risk factors and quality of life. Objective: The objective of the study was to assess CV risk factors and patient-reported outcomes after treatment. Design: This was a randomized, double-blind, crossover study of l-thyroxine and placebo. Setting: The study was conducted with community-dwelling patients. Patients: One hundred patients [mean age (sd) 53.8 (12) yr, 81 females] with SCH [mean TSH 6.6 (1.3) mIU/liter] without previously treated thyroid or vascular disease. Intervention: Intervention consisted of 100 μg l-thyroxine or placebo daily for 12 wk each. Measurements: Primary parameters were total cholesterol (TC) and endothelial function [brachial artery flow-mediated dilatation (FMD)], an early marker of atherosclerosis. Patient-reported outcomes were also assessed. Results:...

Journal ArticleDOI
TL;DR: Resolving the precise nature of the DNA lesions present in the spermatozoa of infertile men will be an important step towards uncovering the aetiology of this damage and developing strategies for its clinical management.
Abstract: DNA damage in the male germline is associated with poor fertilization rates following IVF, defective preimplantation embryonic development, and high rates of miscarriage and morbidity in the offspring, including childhood cancer. This damage is poorly characterized, but is known to involve hypomethylation of key genes, oxidative base damage, endonuclease-mediated cleavage and the formation of adducts with xenobiotics and the products of lipid peroxidation. There are many possible causes of such DNA damage, including abortive apoptosis, the oxidative stress associated with male genital tract infection, exposure to redox cycling chemicals, and defects of spermiogenesis associated with the retention of excess residual cytoplasm. Physical factors such as exposure to radiofrequency electromagnetic radiation or mild scrotal heating can also induce DNA damage in mammalian spermatozoa, although the underlying mechanisms are unclear. Ultimately, resolving the precise nature of the DNA lesions present in the spermatozoa of infertile men will be an important step towards uncovering the aetiology of this damage and developing strategies for its clinical management.

Journal ArticleDOI
TL;DR: Novel rational therapies including antiselectin and antichemokine receptor modalities designed to block eosinophil development and trafficking are discussed, together with the implications of recent clinical studies that have evaluated the efficacy of humanized anti-IL-5 mAb therapy.
Abstract: Blood eosinophilia and tissue eosinophilia are characteristic features of allergic inflammation and asthma, conditions associated with prominent production of TH2 cytokines IL-4, IL-5, and IL-13. In this review, we will consider recent advances in our understanding of the molecular mechanisms that promote expansion and differentiation of eosinophil progenitors in bone marrow, eosinophil recruitment in response to chemokine receptor 3 agonists eosinophil transit mediated by specific ligand-receptor interactions, and prolonged survival of eosinophils in peripheral tissues. Novel rational therapies including antiselectin and antichemokine receptor modalities designed to block eosinophil development and trafficking are discussed, together with the implications of recent clinical studies that have evaluated the efficacy of humanized anti–IL-5 mAb therapy.

Journal ArticleDOI
TL;DR: In this article, the authors provide an overview of coal devolatilization studies, especially the experimental studies and modelling efforts on the formation of char structure of bituminous coals in the open literature.

Journal ArticleDOI
TL;DR: This work discusses both continuous and discrete time cases, and shows that for either state feedback, or for output feedback delay-free, minimum phase plants, there are limitations on the ability to stabilize an unstable plant over an SNR constrained channel.
Abstract: There has recently been significant interest in feedback stabilization problems with communication constraints including constraints on the available data rate. Signal-to-noise ratio (SNR) constraints are one way in which data-rate limits arise, and are the focus of this paper. In both continuous and discrete-time settings, we show that there are limitations on the ability to stabilize an unstable plant over a SNR constrained channel using finite-dimensional linear time invariant (LTI) feedback. In the case of state feedback, or output feedback with a delay-free, minimum phase plant, these limitations in fact match precisely those that might have been inferred by considering the associated ideal Shannon capacity data rate over the same channel. In the case of LTI output feedback, additional limitations are shown to apply if the plant is nonminimum phase. In this case, we show that for a continuous-time nonminimum phase plant, a periodic linear time varying feedback scheme with fast sampling may be used to recover the original SNR requirement at the cost of robustness properties. The proposed framework inherently captures channel noise effects in a simple formulation suited to conventional LTI control performance and robustness analysis, and has potential to handle time delays and bandwidth constraints in a variety of control over communication links problems.

Journal ArticleDOI
TL;DR: The results of this review demonstrate that tests do exist that change the probability of the disc or SIJ (but not the facet joint) as the source of low back pain, however, the changes in probability are usually small and at best moderate.
Abstract: Clinical practice guidelines state that the tissue source of low back pain cannot be specified in the majority of patients. However, there has been no systematic review of the accuracy of diagnostic tests used to identify the source of low back pain. The aim of this systematic review was therefore to determine the diagnostic accuracy of tests available to clinicians to identify the disc, facet joint or sacroiliac joint (SIJ) as the source of low back pain. MEDLINE, EMBASE and CINAHL were searched up to February 2006 with citation tracking of eligible studies. Eligible studies compared index tests with an appropriate reference test (discography, facet joint or SIJ blocks or medial branch blocks) in patients with low back pain. Positive likelihood ratios (+LR) > 2 or negative likelihood ratios (-LR) 2) in the majority of studies increasing the probability of the disc being the low back pain source. However, heterogeneity of the data prevented pooling. +LR ranged from 1.5 to 5.9, 1.6 to 4.0, and 0.6 to 5.9 for high intensity zone, disc degeneration and endplate changes, respectively. Centralisation was the only clinical feature found to increase the likelihood of the disc as the source of pain: +LR = 2.8 (95%CI 1.4-5.3). Absence of degeneration on MRI was the only test found to reduce the likelihood of the disc as the source of pain: -LR = 0.21 (95%CI 0.12-0.35). While single manual tests of the SIJ were uninformative, their use in combination was informative with +LR of 3.2 (95%CI 2.3-4.4) and -LR of 0.29 (95%CI 0.12-0.35). None of the tests for facet joint pain were found to be informative. The results of this review demonstrate that tests do exist that change the probability of the disc or SIJ (but not the facet joint) as the source of low back pain. However, the changes in probability are usually small and at best moderate. The usefulness of these tests in clinical practice, particularly for guiding treatment selection, remains unclear.

Journal ArticleDOI
TL;DR: It is argued that in exploring new sources of bioactive natural products the marine environment warrants particular attention, in view of the remarkable diversity of microorganisms and metabolic products.

Journal ArticleDOI
TL;DR: The relationship between visual estimates of topography and species richness is strongest with fish 10–30 cm total length (TL), abundance of fish within this size category also correlating positively with topographic visual assessments.
Abstract: Visual assessments of topographic habitat structure and benthos on coral reefs were appraised using quantitative data collected from 16 replicate surveys within each of 21 sites on Seychelles reefs. Results from visual assessments of reef benthos were similar to those obtained using techniques frequently used to assess benthic complexity and composition. Visual estimates of habitat topography were correlated with rugosity, reef height and holes of 10–70 cm diameter, whilst visual estimates of benthic composition were very similar to those obtained from line intercept transects. Visual estimates of topography correlated strongly with species richness of fish communities and explained 42% of the variation in these data. The relationship between visual estimates of topography and species richness is strongest with fish 10–30 cm total length (TL), abundance of fish within this size category also correlating positively with topographic visual assessments. Visual techniques are prone to observer bias, however with regular training they can be used to quickly provide a reliable and effective means of assessing habitat complexity and benthos on coral reefs.

Journal ArticleDOI
TL;DR: The data indicate that FTY720 induces apoptosis and impairs clonogenicity of imatinib/dasatinib-sensitive and -resistant p210/p190(BCR/ABL) myeloid and lymphoid cell lines and CML-BC and Ph1 ALL progenitors but not of normal CD34+ andCD34+/CD19+ bone marrow cells.
Abstract: Blast crisis chronic myelogenous leukemia (CML-BC) and Philadelphia chromosome–positive (Ph1-positive) acute lymphocytic leukemia (ALL) are 2 fatal BCR/ABL-driven leukemias against which Abl kinase inhibitors fail to induce a long-term response. We recently reported that functional loss of protein phosphatase 2A (PP2A) activity is important for CML blastic transformation. We assessed the therapeutic potential of the PP2A activator FTY720 (2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol hydrochloride), an immunomodulator in Phase III trials for patients with multiple sclerosis or undergoing organ transplantation, in CML-BC and Ph1 ALL patient cells and in in vitro and in vivo models of these BCR/ABL+ leukemias. Our data indicate that FTY720 induces apoptosis and impairs clonogenicity of imatinib/dasatinib-sensitive and -resistant p210/p190BCR/ABL myeloid and lymphoid cell lines and CML-BCCD34+ and Ph1 ALLCD34+/CD19+ progenitors but not of normal CD34+ and CD34+/CD19+ bone marrow cells. Furthermore, pharmacologic doses of FTY720 remarkably suppress in vivo p210/p190BCR/ABL-driven [including p210/p190BCR/ABL (T315I)] leukemogenesis without exerting any toxicity. Altogether, these results highlight the therapeutic relevance of rescuing PP2A tumor suppressor activity in Ph1 leukemias and strongly support the introduction of the PP2A activator FTY720 in the treatment of CML-BC and Ph1 ALL patients.

Journal ArticleDOI
01 Mar 2007-Thorax
TL;DR: There is evidence of activation of the innate immune system in asthma which results in the production of pro-inflammatory cytokines and may contribute to the pathogenesis of neutrophilic asthma.
Abstract: Background: The role of the innate immune system in the pathogenesis of asthma is unclear. Activation of innate immune receptors in response to bacterial lipopolysaccharide, viral infection and particulate matter triggers a pre-programmed inflammatory response, which involves interleukin (IL)8 and neutrophil influx. The inflammatory response in asthma is heterogeneous. Aim: To test the hypothesis that innate immune activation may be a relevant inflammatory mechanism in neutrophilic asthma where IL8 levels are increased. Methods: Induced sputum was obtained from non-smoking adults with asthma (n = 49), healthy controls (n = 13) and a positive reference group with bronchiectasis (n = 9). Subjects with asthma were classified into inflammatory subtypes using induced sputum cell counts. Sputum was examined for mRNA expression of the innate immune receptors toll-like receptor (TLR)2, TLR4 and CD14, and inflammatory cytokines. A separate sputum portion was dispersed and the supernatant assayed for surfactant protein A, IL8, soluble CD14 and endotoxin. Results: Expression of innate immune receptors was increased in subjects with bronchiectasis and neutrophilic asthma compared with other asthma subtypes and controls. Increased expression of the receptors TLR2, TLR4 and CD14, as well as the pro-inflammatory cytokines IL8 and IL1β, was observed. Subjects with neutrophilic asthma had higher airway levels of endotoxin than the other groups studied. Conclusion: There is evidence of activation of the innate immune system in asthma which results in the production of pro-inflammatory cytokines and may contribute to the pathogenesis of neutrophilic asthma.

Journal ArticleDOI
TL;DR: The results indicate that the unfished "equilibrium" biomass of the fish assemblage > 10 cm is 1100-1200 kg/ha, but these small parks are likely to underestimate pre-human influence values due to edge effects and the rarity of taxa with large area requirement, such as apex predators, including sharks.
Abstract: Identifying the rates of recovery of fish in no-take areas is fundamental to designing protected area networks, managing fisheries, estimating yields, identifying ecological interactions, and informing stakeholders about the outcomes of this management. Here we study the recovery of coral reef fishes through 37 years of protection using a space-for-time chronosequence of four marine national parks in Kenya. Using AIC model selection techniques, we assessed recovery trends using five ecologically meaningful production models: asymptotic, Ricker, logistic, linear, and exponential. There were clear recovery trends with time for species richness, total and size class density, and wet masses at the level of the taxonomic family. Species richness recovered rapidly to an asymptote at 10 years. The two main herbivorous families displayed differing responses to protection, scarids recovering rapidly, but then exhibiting some decline while acanthurids recovered more slowly and steadily throughout the study. Recovery of the two invertebrate-eating groups suggested competitive interactions over resources, with the labrids recovering more rapidly before a decline and the balistids demonstrating a slower logistic recovery. Remaining families displayed differing trends with time, with a general pattern of decline in smaller size classes or small-bodied species after an initial recovery, which suggests that some species- and size-related competitive and predatory control occurs in older closures. There appears to be an ecological succession of dominance with an initial rapid rise in labrids and scarids, followed by a slower rise in balistids and acanthurids, an associated decline in sea urchins, and an ultimate dominance in calcifying algae. Our results indicate that the unfished ''equilibrium'' biomass of the fish assemblage .10 cm is 1100-1200 kg/ha, but these small parks (,10 km 2 ) are likely to underestimate pre- human influence values due to edge effects and the rarity of taxa with large area requirement, such as apex predators, including sharks.

Journal ArticleDOI
TL;DR: Long-term follow-up of this older population confirms that the risk of ARM progression is related strongly to the severity of early-stage lesions, and provides evidence-based criteria for identifying persons at high risk of developing late ARM.