Children's Research Institute Research Articles

The Pragmatic Reality of Clinical Research

Journal Article The Pragmatic Reality of Clinical Research Get access Helen Shoemark, PhD Helen Shoemark, PhD Career Development Fellow, Senior Music Therapist (Neonatology), Adjunct Professor, Honorary Senior Fellow Murdoch Childrens Research Institute, Melbourne AustraliaThe Royal Children's HospitalMelbourneUniversity of QueenslandUniversity of Melbourne Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Music Therapy, Volume 50, Issue 3, Fall 2013, Pages 150–154, https://doi.org/10.1093/jmt/50.3.150 Published: 01 October 2013

Mass Spectrometry Imaging of Sphingolipids in Preeclamptic Placentae

Mass Spectrometry Imaging of Sphingolipids in Preeclamptic Placentae

Correction: Two ENU-Induced Alleles of Atp2b2 Cause Deafness in Mice

The name of the fourth author was given incorrectly. The correct name is: Rachel A. Burt. The correct citation is: Carpinelli MR, Manning MG, Kile BT, Burt RA (2013) Two ENU-Induced Alleles of Atp2b2 Cause Deafness in Mice. PLoS ONE 8(6): e67479. doi:10.1371/journal.pone.0067479. In addition, affiliations for the fourth author were missing. Rachel A. Burt is not only affiliated with institutions 1, Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, Victoria, Australia and 4, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia, but also institutions 2, The HEARing Cooperative Research Centre, University of Melbourne, Melbourne, Victoria, Australia, and 3, Department of Genetics, University of Melbourne, Melbourne, Victoria, Australia.

Wave reflection and central pressure augmentation

aHeart Research Group, Murdoch Childrens Research Institute bDepartment of Paediatrics, University of Melbourne, Melbourne, Australia cBiomedical Simulation Laboratory, University of Toronto, Toronto, Canada Correspondence to Jonathan Mynard, B.Sc., B.Eng., M.Res., Ph.D., Murdoch Childrens Research Institute, Flemington Rd., Parkville, Victoria, 3052, Australia. E-mail: [email protected]

Technical and functional validations of High Angular Resolution Diffusion Imaging (HARDI)-MR tractography in paediatric epilepsy patients

Event Abstract Back to Event Technical and functional validations of High Angular Resolution Diffusion Imaging (HARDI)-MR tractography in paediatric epilepsy patients Sarah M. Barton1*, Joseph Y. Yang2, Wirginia Maixner2, A. Simon Harvey3, 4, Jeremy Freeman3, Richard Beare1, Marc Seal1, 4 and Vicki Anderson4, 5, 6 1 Murdoch Childrens Research Institute, Developmental Imaging, Australia 2 The Royal Children’s Hospital, Department of Neurosurgery, Australia 3 The Royal Children’s Hospital, Department of Neurology, Australia 4 The University of Melbourne, Department of Paediatrics, Australia 5 Murdoch Childrens Research Institute, Child Neuropsychology, Australia 6 The University of Melbourne, School of Psychological Sciences, Australia Background: HARDI-MR tractography is a neuroimaging technique that allows modelling of white matter tracts in the brain. The ability to visualise white matter tracts pre-operatively has the potential to improve neurosurgery accuracy and outcome. However despite its growing popularity, questions remain regarding its technical reproducibility and validity in routine clinical use. Here we examine the reliability of a locally practised HARDI-MR tractography method in paediatric epilepsy patients and in a novel demonstration present the functional validation of the technique against multimodal clinical investigations. Methods: Eight patients were identified retrospectively from our Children’s Epilepsy Program database. All cases had pre-operative diffusion MRI sequences and motor and/or language functional MRI (fMRI). In select cases, intra- or extra-operative motor and/or language cortical mapping results were available. Corticospinal (CST) and superior longitudinal fasciculus (SLF) tracts were generated by two different operators. Coefficients of variation (CV), intra-class correlation coefficients (ICC) and dice similarity coefficients (DSC) were calculated to assess reproducibility of tract metrics and degree of tract overlap between the operators. Tractography results were compared to fMRI activation, cortical mapping results and the patient’s clinical assessment findings. Results: All white matter tracts generated were visually comparable between operators. The tract measures showed low CV values, high ICC values and high DSC scores, indicating there was a high degree of reproducibility and overlap within and between the two operators. Cortical origin and terminations of all CST and SLF tracts matched with the patient’s areas of motor or language fMRI activation. In all but one case, tractography results matched cortical stimulation findings. Tracts were also compatible with the clinical assessment findings. Discussion: In a group of paediatric epilepsy patients, tractography results could be reliably generated and reproduced. In a novel demonstration, there was correspondence between the anatomical course of the tracts with areas of fMRI activation and, in all but one case, cortical stimulation findings. This suggests that in experienced hands, HARDI-MR tractography can be a reliable and valid technique in clinical settings. HARDI-MR tractography has the potential to make valuable contributions to neurosurgery planning to improve outcome for patients. Keywords: tractography, corticospinal tract, Superior longitudinal fasciculus, Paediatric, Epilepsy, Neurosurgery, diffusion imaging Conference: ACNS-2013 Australasian Cognitive Neuroscience Society Conference, Clayton, Melbourne, Australia, 28 Nov - 1 Dec, 2013. Presentation Type: Poster Topic: Other Citation: Barton SM, Yang JY, Maixner W, Harvey A, Freeman J, Beare R, Seal M and Anderson V (2013). Technical and functional validations of High Angular Resolution Diffusion Imaging (HARDI)-MR tractography in paediatric epilepsy patients. Conference Abstract: ACNS-2013 Australasian Cognitive Neuroscience Society Conference. doi: 10.3389/conf.fnhum.2013.212.00059 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 15 Oct 2013; Published Online: 25 Nov 2013. * Correspondence: Dr. Sarah M Barton, Murdoch Childrens Research Institute, Developmental Imaging, Parkville, Victoria, Australia, sarah.barton@mcri.edu.au Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Sarah M Barton Joseph Y Yang Wirginia Maixner A. Simon Harvey Jeremy Freeman Richard Beare Marc Seal Vicki Anderson Google Sarah M Barton Joseph Y Yang Wirginia Maixner A. Simon Harvey Jeremy Freeman Richard Beare Marc Seal Vicki Anderson Google Scholar Sarah M Barton Joseph Y Yang Wirginia Maixner A. Simon Harvey Jeremy Freeman Richard Beare Marc Seal Vicki Anderson PubMed Sarah M Barton Joseph Y Yang Wirginia Maixner A. Simon Harvey Jeremy Freeman Richard Beare Marc Seal Vicki Anderson Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Language and communication in children with agenesis of the corpus callosum

Event Abstract Back to Event Language and communication in children with agenesis of the corpus callosum Vanessa Siffredi1, 2, 3*, Alissandra McIlroy1, 2, Vicki Anderson1, 2, 4, Richard Leventer1, 2, 4, Amanda Wood5 and Megan M. Spencer-Smith1, 6 1 Murdoch Childrens Research Institute, Australia 2 The University of Melbourne, Australia 3 The University of Geneva, Switzerland 4 The Royal Children's Hospital, Australia 5 University of Birmingham, United Kingdom 6 Swinburne University of Technology, Australia Background Expressive and receptive language are predominantly processed by the left hemisphere. Interhemispheric transfer is important for the integration of linguistic and communication related information. The corpus callosum, the largest white matter pathway connecting the two cerebral hemispheres, plays a crucial role in the transfer and integration of language and communication information across hemispheres. Developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation resulting from disruption of corpus callosum formation. This study aims to: 1) describe language and communication skills in children with AgCC; and 2) examine the role of general intellectual ability, brain structure (partial or complete AgCC; intactness of anterior and posterior commissures) and clinical factors (presence of seizure disorder, genetic condition) as predictors of language and communication abilities. Methods Fifteen children with AgCC (partial n=8, complete n=7) aged 8 to 15 years (M= 12.03, SD=2.16) were recruited. Language (receptive and expressive skills), general intellectual and communication abilities were estimated using standardised measures. Brain MRI was reviewed using a standardised coding system. Results Preliminary analysis showed that children with AgCC performed below the test mean on all measures: expressive (p=.001), receptive (p=.001), communication (p=.005). There was some variability in language and communication skills: communication ratings were higher than expressive language scores (p=.015), which were higher than receptive language scores (p=.016). A series of regressions showed that general intellectual ability predicted expressive language scores (p=.001), and approached significance for receptive language scores (p=.064). Intactness of the corpus callosum predicted communication ratings (p=.043), with complete AgCC associated with poorer outcomes. Clinical factors and intactness of anterior and posterior commissures were not significantly associated with language and communication abilities. Discussion Language and communication abilities are reduced in children with AgCC. Contrary to expectations, children with AgCC showed better communication than language abilities, with greatest difficulties in expressive language. General intellectual ability predicted language but not communication abilities. The intactness of the corpus callosum predicted communication but not language abilities. Acknowledgements This study was supported by the Victorian Government’s Operational Infrastructure Support Program; by the Murdoch Childrens Research Institute; and by the Swiss National Science Foundation (SNSF). Keywords: Agenesis of the Corpus callosum, Language, Communication, MRI, developmental neuropsychology Conference: ACNS-2013 Australasian Cognitive Neuroscience Society Conference, Clayton, Melbourne, Australia, 28 Nov - 1 Dec, 2013. Presentation Type: Oral Topic: Language Citation: Siffredi V, McIlroy A, Anderson V, Leventer R, Wood A and Spencer-Smith MM (2013). Language and communication in children with agenesis of the corpus callosum. Conference Abstract: ACNS-2013 Australasian Cognitive Neuroscience Society Conference. doi: 10.3389/conf.fnhum.2013.212.00151 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 15 Oct 2013; Published Online: 25 Nov 2013. * Correspondence: Ms. Vanessa Siffredi, Murdoch Childrens Research Institute, Melbourne, Australia, vanessa.siffredi@mcri.edu.au Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Vanessa Siffredi Alissandra McIlroy Vicki Anderson Richard Leventer Amanda Wood Megan M Spencer-Smith Google Vanessa Siffredi Alissandra McIlroy Vicki Anderson Richard Leventer Amanda Wood Megan M Spencer-Smith Google Scholar Vanessa Siffredi Alissandra McIlroy Vicki Anderson Richard Leventer Amanda Wood Megan M Spencer-Smith PubMed Vanessa Siffredi Alissandra McIlroy Vicki Anderson Richard Leventer Amanda Wood Megan M Spencer-Smith Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

LONG-TERM FOLLOW UP STUDY TO THE FIJI PNEUMOCOCCAL PROJECT: INVESTIGATION OF IMMUNE HYPORESPONSIVENESS FOLLOWING A 12-MONTH PNEUMOCOCCAL POLYSACCHARIDE BOOSTER

Event Abstract Back to Event LONG-TERM FOLLOW UP STUDY TO THE FIJI PNEUMOCOCCAL PROJECT: INVESTIGATION OF IMMUNE HYPORESPONSIVENESS FOLLOWING A 12-MONTH PNEUMOCOCCAL POLYSACCHARIDE BOOSTER Paul V. Licciardi1, 2*, Elizabeth A. Clutterbuck3, Anne Balloch1, Zheng Quan Toh1, Kathryn Bright1, Fiona M. Russell2, 4, Mimi L. Tang1, 2, 5, Andrew J. Pollard3, 6 and Edward K. Mulholland1, 7, 8 1 Murdoch Childrens Research Institute, Pneumococcal Research, Australia 2 University of Melbourne, Department of Paediatrics, Australia 3 University of Oxford, Centre for Clinical Vaccinology and Tropical Medicine, United Kingdom 4 University of Melbourne, Centre of International Child Health, Australia 5 Royal Children's Hospital, Department of Allergy and Immunology, Australia 6 University of Oxford, Department of Paediatrics, United Kingdom 7 Menzies School of Health Research, Australia 8 London School of Hygiene and Tropical Medicine, United Kingdom Background & Aim: The Fiji Pneumococcal Project (FiPP) examined the immunogenicity of reduced dose schedules comprising pneumococcal conjugate (PCV) and polysaccharide (PPS) vaccines. Following a micro-PPS (20%) challenge dose at 17 months, children that received the PPS at 12 months age exhibited immune hyporesponsiveness in terms of serotype-specific IgG and opsonophagocytic (OPA) levels. The 12-month PPS dose also had no impact on vaccine-type carriage. Methods: This was a follow-up study to examine the long-term immunological impact of the 12-month PPS booster. Blood samples were taken pre- and 28-days post-PCV13 immunisation from the first 101 children (now 4-6 years old) re-consented into this study. To date, analysis includes specific IgG measurement to all 23 serotypes in PPS as well enumeration of the memory B cell response to serotypes 1, 3, 4, 6B, 14, 19F and 23F. Results: Significantly lower pre-PCV13 IgG levels for 6B (p=0.003), 22F (p=0.024) and 23F (borderline p=0.053) were detected in children that received the 12-month PPS; after PCV13, only serotype 22F IgG was lower in PPS-vaccinated children compared to those that weren’t (p=0.009). Memory B cell responses were not different before PCV13, however a significantly lower number of 23F-specific B cells (p=0.021) post-PCV13 were found in children given PPS at 12 months of age. Conclusion: With the exception of a few serotype, immune hyporesponsiveness was no longer observed before or after PCV13 vaccination. Analysis is ongoing to evaluate the impact of the PPS booster in this study. Keywords: immune hyporesponsiveness, memory B cell, Polysaccharides, Bacterial, pneumococcus, Pneumococcal Vaccines Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Adaptive Immunity Citation: Licciardi PV, Clutterbuck EA, Balloch A, Toh Z, Bright K, Russell FM, Tang ML, Pollard AJ and Mulholland EK (2013). LONG-TERM FOLLOW UP STUDY TO THE FIJI PNEUMOCOCCAL PROJECT: INVESTIGATION OF IMMUNE HYPORESPONSIVENESS FOLLOWING A 12-MONTH PNEUMOCOCCAL POLYSACCHARIDE BOOSTER. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00672 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Paul V Licciardi, Murdoch Childrens Research Institute, Pneumococcal Research, Melbourne, Australia, paul.licciardi@mcri.edu.au Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Paul V Licciardi Elizabeth A Clutterbuck Anne Balloch Zheng Quan Toh Kathryn Bright Fiona M Russell Mimi L Tang Andrew J Pollard Edward K Mulholland Google Paul V Licciardi Elizabeth A Clutterbuck Anne Balloch Zheng Quan Toh Kathryn Bright Fiona M Russell Mimi L Tang Andrew J Pollard Edward K Mulholland Google Scholar Paul V Licciardi Elizabeth A Clutterbuck Anne Balloch Zheng Quan Toh Kathryn Bright Fiona M Russell Mimi L Tang Andrew J Pollard Edward K Mulholland PubMed Paul V Licciardi Elizabeth A Clutterbuck Anne Balloch Zheng Quan Toh Kathryn Bright Fiona M Russell Mimi L Tang Andrew J Pollard Edward K Mulholland Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents

Histone deacetylase (HDAC) inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents) as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza) and depsipeptide (romidepsin, Istodax). More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the advancement of these drugs, especially to facilitate the rational design of HDAC inhibitors that are effective as antineoplastic agents. This review will discuss the use of HDAC inhibitors as multitargeted therapies for malignancy. Further, we outline the pharmacology and mechanisms of action of HDAC inhibitors while discussing the safety and efficacy of these compounds in clinical studies to date.

Nasogastric hydration versus intravenous hydration for infants with bronchiolitis: a randomised trial

Bronchiolitis is the most common lower respiratory tract infection in infants and the leading cause of hospital admission. Hydration is a mainstay of treatment, but insufficient evidence exists to guide clinical practice. We aimed to assess whether intravenous hydration or nasogastric hydration is better for treatment of infants. In this multicentre, open, randomised trial, we enrolled infants aged 2-12 months admitted to hospitals in Australia and New Zealand with a clinical diagnosis of bronchiolitis during three bronchiolitis seasons (April 1-Oct 31, in 2009, 2010, and 2011). We randomly allocated infants to nasogastric hydration or intravenous hydration by use of a computer-generated sequence and opaque sealed envelopes, with three randomly assigned block sizes and stratified by hospital site and age group (2-<6 months vs 6-12 months). The primary outcome was length of hospital stay, assessed in all randomly assigned infants. Secondary outcomes included rates of intensive-care unit admission, adverse events, and success of insertion. This trial is registered with the Australian and New Zealand clinical trials registry, ACTRN12605000033640. Mean length of stay for 381 infants assigned nasogastric hydration was 86·6 h (SD 58·9) compared with 82·2 h (58·8) for 378 infants assigned intravenous hydration (absolute difference 4·5 h [95% CI -3·9 to 12·9]; p=0·30). Rates of admission to intensive-care units, need for ventilatory support, and adverse events did not differ between groups. At randomisation, seven infants assigned nasogastric hydration were switched to intravenous hydration and 56 infants assigned intravenous hydration were switched to nasogastric hydration because the study-assigned method was unable to be inserted. For those infants who had data available for successful insertion, 275 (85%) of 323 infants in the nasogastric hydration group and 165 (56%) of 294 infants in the intravenous hydration group required only one attempt for successful insertion. Intravenous hydration and nasogastric hydration are appropriate means to hydrate infants with bronchiolitis. Nasogastric insertion might require fewer attempts and have a higher success rate of insertion than intravenous hydration. Australian National Health and Medical Research Council, Samuel Nissen Charitable Foundation (Perpetual), Murdoch Children's Research Institute, Victorian Government.

Journal-related Activities and Other Special Activities at the 2012 American Society of Anesthesiologists Annual Meeting

Journal-related Activities and Other Special Activities at the 2012 American Society of Anesthesiologists Annual Meeting

Erratum to: Genetic Counseling and Testing for FMR1 Gene Mutations: Practice Guidelines of the National Society of Genetic Counselors

Erratum to: J Genet Counsel DOI 10.1007/s10897-012-9524-8 The research affiliation of author Alison D. Archibald was omitted from the publication. Murdoch Childrens Research Institute, Melbourne, Victoria, Australia

O-005

University of Washington, Seattle Children's Research Institute [email protected] Seattle Children's Research Institute, USA Mount SInai School of Medicine, USA MN

Letter to the Editor regarding ‘effect of rivaroxaban, in contrast to heparin, is similar in neonatal and adult plasma’

aMurdoch Childrens Research Institute bDepartment of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia Correspondence to Dr Vera Ignjatovic, PhD, Senior Research Fellow, Haematology Research Laboratory, Murdoch Childrens Research Institute, Royal Children's Hospital Flemington Road, Parkville, Victoria, 3052, AustraliaTel: +61 3 99366520; e-mail: [email protected]

Sleep Problems in Children with Fetal Alcohol Spectrum Disorders

Sleep problems in children with fetal alcohol spectrum disorders (FASD) are reportedly common but not well characterized. Objectives were to: (1) assess sleep concerns in children with FASD using a caregiver-report survey, the Children's Sleep Habits Questionnaire (CSHQ); (2) compare CSHQ results with those of previously reported community sample; and (3) describe pilot polysomnography findings in children with FASD. Children with FASD were recruited from a behavioral intervention study, and participating caregivers completed the CSHQ. CSHQ results were compared with the original data from a previously published community sample of similar age. Participants with FASD and elevated CSHQ scores were offered overnight polysomnography. Thirty-three children with FASD (4.1-12.1 years) were enrolled; 85% of children with FASD scored above the clinical cutoff Total Score of 41, reflecting marked sleep disturbance. Elevated subdomain scores occurred primarily in areas concerning for pediatric insomnia. Those with comorbid ADHD had elevated CSHQ on additional subdomains with no difference in Total Scores. Compared with the community sample, children with FASD had higher Total Scores on the CSHQ (52 vs. 39, p < 0.001). Polysomnography, completed in 5 subjects, revealed mild sleep disordered breathing and fragmented sleep with elevated non-respiratory arousal indices. Clinically significant sleep problems are present in children with FASD on both subjective and objective measures. Further investigation is needed to better describe these sleep disturbances and their impact on overall health and daytime neurobehavioral problems in this clinical population.

Non‐invasive fetal genome sequencing: Opportunities and challenges

Non‐invasive fetal genome sequencing: Opportunities and challenges

Reply

Internal Medicine JournalVolume 42, Issue 8 p. 961-962 Reply R. M. Lucas, R. M. Lucas National Centre for Epidemiology and Population Health, The Australian National University, Canberra, ACTSearch for more papers by this authorJ. K. C. Lai, J. K. C. Lai National Centre for Epidemiology and Population Health, The Australian National University, Canberra, ACTSearch for more papers by this authorE. Banks, E. Banks National Centre for Epidemiology and Population Health, The Australian National University, Canberra, ACTSearch for more papers by this authorA.-L. Ponsonby, A.-L. Ponsonby Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, AustraliaSearch for more papers by this author R. M. Lucas, R. M. Lucas National Centre for Epidemiology and Population Health, The Australian National University, Canberra, ACTSearch for more papers by this authorJ. K. C. Lai, J. K. C. Lai National Centre for Epidemiology and Population Health, The Australian National University, Canberra, ACTSearch for more papers by this authorE. Banks, E. Banks National Centre for Epidemiology and Population Health, The Australian National University, Canberra, ACTSearch for more papers by this authorA.-L. Ponsonby, A.-L. Ponsonby Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, AustraliaSearch for more papers by this author First published: 21 August 2012 https://doi.org/10.1111/j.1445-5994.2012.02859.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume42, Issue8August 2012Pages 961-962 RelatedInformation

Editorial introductions

Editorial introductions

Corrigendum to “SPIRE: Systematic Protein Investigative Research Environment” [J. Proteomics 75 (1) (2011) 122–126

Eugene Kolker b, c, d, ⁎, Roger Higdon b, , Dean Welch , Andrew Bauman , Elizabeth Stewart , Winston Haynes , William Broomall , Natali Kolker c Bioinformatics & High-throughput Analysis Laboratory, Seattle Children's Research Institute, Seattle, WA, USA High-throughput Analysis Core, Seattle Children's Research Institute, Seattle, WA, USA Predictive Analytics, Seattle Children's Hospital, Seattle, WA, USA Department of Pediatrics, University of Washington, Seattle, WA, USA Department of Medical Education & Biomedical Informatics, University of Washington, Seattle, WA, USA

Yet Another Reason to Treat HIV Infection

Antiretroviral therapy (ART) has allowed a cohort of children who were perinatally infected with human immunodeficiency virus (HIV) to reach early adulthood, but their risk of death, non-AIDS-defining infections, cancers and organ failure remain elevated compared with uninfected populations [1]. Although ART dramatically improves the survival of infants [2] and children [1] and appears to improve the growth and neurologic function when initiated in older children [3, 4], less is known about the optimal time to initiate ART in older, asymptomatic children to prevent indolent HIV-associated morbidities, including loss of cognitive functions. The recommended CD4 cell count at which to start ART in adults and adolescents has been progressively revised upward [5]; however, this threshold remains controversial, and resulted in the split judgment by the 2011 Department of Health and Human Services panel on whether to recommend ART for all adults [5]. Current World Health Organization guidelines recommend the use of adult immunologic criteria (CD4 cell count, ,350 cells/lL) to determine when to initiate ART in children .5 years of age [6]. This leaves many relatively asymptomatic HIV-infected children with moderately decreased CD4 T-cell counts untreated, which could place them at risk for HIV-associated morbidity. (Normal CD4 cell counts in children 5–12 years of age range from 980 to 1200 cells/lL [7, 8]). In this issue of Clinical Infectious Diseases, Ruel et al [9] present a casecontrol study that demonstrates neurocognitive and motor dysfunction in ‘‘asymptomatic’’ HIV-infected children 6–12 years of age who do not qualify for ART. Their findings suggest that the World Health Organization guidelines do not capture early neurologic disease and provide a rationale to explore whether earlier ART would benefit these children. In children, progressive HIV encephalopathy (PHE) is a severe, potentially fatal, AIDS-defining illness that was common in the pre-ART era. It is defined as failure to achieve developmental milestones, or loss of previously acquired developmental milestones, impaired brain growth, and acquired symmetrical motor deficits (manifested by $2 of the following: paresis, pathologic reflexes, ataxia or gait disturbance) [10]. In the pre-ART era, the prevalence of PHE was 30%–50% [11]. With the use of ART, symptoms of those affected by PHE generally have improved, fatalities have become uncommon, and the incidence of PHE has dropped 10-fold [4, 11]. The study by Ruel et al carefully assessed neurocognitive and motor function in HIV-infected African children who did not qualify for ART and who were not considered encephalopathic by their referring physicians. The study used neurocognitive tests (Test of Variables of Attention [TOVA]; the Kaufman Assessment Battery for Children, 2nd edition [KABC-2]; and the Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition [BOT-2]) to detect impairments in attention deficit and impulsivity, cognition, and motor function, respectively. The study does not provide an estimate of the prevalence of neurocognitive impairment but identifies subtle population-level differences between HIV-infected and uninfected children. This study is noteworthy because it suggests that, unlike PHE, which is rare in the era of ART, subtle neurocognitive and motor impairments affect a significant proportion of apparently asymptomatic HIV-infected children who do not yet qualify for ART. Unfortunately, the large-scale administration of the neurocognitive tests used by Ruel et al to prompt ART initiation is unrealistic in low resource settings owing to the time, space, and trained personnel needed for testing. Ideally, biomarkers and/or simple tests would identify early symptoms of neuropathology and serve as tools to monitor children who do not qualify for ART. Received 1 December 2011; accepted 9 December 2011. Correspondence: Lisa M. Frenkel, MD, Department of Pediatrics, Laboratory Medicine and Global Health, University of Washington, Children's Hospital and Research Institute, 1900 Ninth Avenue, Seattle, WA 98101-1304 (lfrenkel@uw.edu). Clinical Infectious Diseases The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@ oup.com. DOI: 10.1093/cid/cir1041

Research performance evaluation: the experience of an independent medical research institute

Evaluation of the social and economic outcomes of health research funding is an area of intense interest and debate. Typically, approaches have sought to assess the impact of research funding by medical charities or regional government bodies. Independent research institutes have a similar need for accountability in investment decisions but have different objectives and funding, thus the existing approaches are not appropriate. An evaluation methodology using eight indicators was developed to assess research performance across three broad categories: knowledge creation; inputs to research; and commercial, clinical and public health outcomes. The evaluation approach was designed to provide a balanced assessment across laboratory, clinical and public health research. With a diverse research agenda supported by a large number of researchers, the Research Performance Evaluation process at the Murdoch Childrens Research Institute has, by necessity, been iterative and responsive to the needs of the Institute and its staff. Since its inception 5 years ago, data collection systems have been refined, the methodology has been adjusted to capture appropriate data, staff awareness and participation has increased, and issues regarding the methodology and scoring have been resolved. The Research Performance Evaluation methodology described here provides a fair and transparent means of disbursing internal funding. It is also a powerful tool for evaluating the Institute's progress towards achieving its strategic goals, and is therefore a key driver for research excellence.