Managing challenges in congenital CMV : current thinking

Congenital human cytomegalovirus (CMV) infection is the most common congenital infection, affecting around 1 in 200 infants in high-income settings. It can have life-long consequences for up to one in four children, including sensorineural hearing loss and neurodisability. Despite the frequency of congenital CMV and the severity for some children, it is a little-known condition by pregnant women, families and healthcare providers. Timely diagnosis of CMV infection in pregnancy is important to facilitate consideration of treatment with valaciclovir, which may reduce the risk of transmission to the fetus or reduce the severity of the outcomes for infected infants. Recognition of features of congenital CMV is important for neonatologists, paediatricians and audiologists to prompt testing for congenital CMV within the first 21 days of life. Early diagnosis gives the opportunity for valganciclovir treatment, where appropriate, to improve outcomes for affected infants. Further research is urgently needed to inform decisions about antenatal and neonatal screening, long-term outcomes for asymptomatic and symptomatic infants, predictors of these outcomes and optimal treatment for women and infants

Biomarkers of Nutrition for Development (BOND)—Iron Review

This is the fifth in the series of reviews developed as part of the Biomarkers of Nutrition for Development (BOND) program. The BOND Iron Expert Panel (I-EP) reviewed the extant knowledge regarding iron biology, public health implications, and the relative usefulness of currently available biomarkers of iron status from deficiency to overload. Approaches to assessing intake, including bioavailability, are also covered. The report also covers technical and laboratory considerations for the use of available biomarkers of iron status, and concludes with a description of research priorities along with a brief discussion of new biomarkers with potential for use across the spectrum of activities related to the study of iron in human health. The I-EP concluded that current iron biomarkers are reliable for accurately assessing many aspects of iron nutrition. However, a clear distinction is made between the relative strengths of biomarkers to assess hematological consequences of iron deficiency versus other putative functional outcomes, particularly the relationship between maternal and fetal iron status during pregnancy, birth outcomes, and infant cognitive, motor and emotional development. The I-EP also highlighted the importance of considering the confounding effects of inflammation and infection on the interpretation of iron biomarker results, as well as the impact of life stage. Finally, alternative approaches to the evaluation of the risk for nutritional iron overload at the population level are presented, because the currently designated upper limits for the biomarker generally employed (serum ferritin) may not differentiate between true iron overload and the effects of subclinical inflammation

Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) – a natural experiment (protocol)

Hepatitis C virus (HCV) is the second largest contributor to liver disease in the UK, with injecting drug use as the main risk factor among the estimated 200 000 people currently infected. Despite effective prevention interventions, chronic HCV prevalence remains around 40% among people who inject drugs (PWID). New direct-acting antiviral (DAA) HCV therapies comine high cure rates (>90%) and short treatment duration (8 to 12 weeks). Theoretical mathematical modelling evidence suggests HCV treatment scale-up can prevent transmission and substantially reduce HCV prevalence/incidence among PWID. Our primary aim is to generate empirical evidence on the effectiveness of HCV ‘Treatment as Prevention’ (TasP) in PWID

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

The Crisis in Timor-Leste: Understanding the Past, Imagining the Future

This book offers a collection of papers originating in a symposium, 'The Crisis in Timor-Leste: Understanding the Past, Imagining the Future', held at Charles Darwin University on 13 November 2006. Together, the papers in this volume address the historical, social and political causes of unrest in Timor-Leste, explaining the violence and rebellion of 2006 in a larger context. By doing this they identify ways to respond to the causes of unrest, particularly the social and developmental strategies the East Timorese can pursue in order to negotiate the transition to a stable, democratic and viable state. Contributors: James Cotton, Jennifer Drysdale, Steven Farram, Trevor Le Lievre, Andrew McWilliam, Ron May, David Mearns, Rod Nixon, Kate Reid-Smith, Dennis Shoesmith.PART ONE: 1 CHALLENGES TO THE STATE -- State Building in Weak States: Some Reflections on the Australian Experience / Ronald J. May -- Crisis of the Timor-Leste State in Comparative Perspective / James Cotton -- Timor-Leste: Interpreting Violence in a Post-Conflict State / Dennis Shoesmith -- PART TWO: CHALLENGES TO CIVIL SOCIETY -- East and West in Timor-Leste: Is there an Ethnic Divide? / Andrew McWilliam -- Masking the Pain: Nation Building and 'Local Anaesthetic' in Timor-Leste / David Mearns -- PART THREE: TIMOR-LESTE AND THE INTERNATIONAL COMMUNITY -- Australian Interest in Timor: A Historical Overview / Steven Farram -- Crocodile Oil: Dragon's Treasure -- A Possible Future Southeast Asian Geopolitical Diaspora? / Kate Reid-Smith -- PART FOUR: CHALLENGES OF GROWTH AND DEVELOPMENT -- Institutional Challenges of Managing Timor-Leste's Petroleum Revenue / Jennifer Drysdale -- Petroleum Sector Investment and Sovereign Risk Perception in East Timor / Trevor Le Lievre -- Challenges for Managing State Agricultural Land and Promoting Post-Subsistence Primary Industry Development in East Timor / Rod Nixon.Jira Ticket : CDU-71 : Collection Development Manager made the decision that for the books that have this message " This book is copyright. Apart from any fair dealing to the purpose of private study, research, criticism or review as permitted under the Copyright Act, no part may be reproduced, by any process, without written permission. Enquiries should be made to the publisher, Charles Darwin University Press, Charles Darwin University, Darwin NT 0909, Australia" in the front they would treat CDU NTU Press as the copyright holder based on this statement. CDU Press have given permission for these to be added to our site but no additional licencing terms provided. That is a reasonable risk management based decision.To purchase this book online visit the CDU Press website via the link below

4-Amino derivatives of the Hsp90 inhibitor CCT018159

4-Amino derivatives of the Hsp90 inhibitor CCT018159 Novel piperazinyl, morpholino and piperidyl derivatives of the pyrazole-based Hsp90 inhibitor CCT018159 are described. Structure-activity relationships have been elucidated by X-ray co-crystal analysis of the new Compounds bound to the N-terminal domain of human Hsp90. Key features of the binding mode are essentially identical to the recently reported potent analogue VER-49009. The most potent of the new compounds has a methylsulfonylbenzyl substituent appended to the piperazine nitrogen, possesses an IC50 of less than 600 nM binding against the enzyme and demonstrates low micromolar inhibition of tumour cell proliferation. (C) 2006 Elsevier Ltd. All rights reserved