Publications by authors named "James D Cooper"

21 Publications

  • Page 1 of 1

Symptomatic pulmonary embolus after catheter removal in children with catheter related thrombosis: A report from the CHAT Consortium.

J Thromb Haemost 2021 Oct 8. Epub 2021 Oct 8.

Departments of Pediatrics and Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Background: Appropriate timing of central venous catheter (CVC) removal, in relation to start of anticoagulation, in children after the diagnosis of a CVC-related thrombosis (CRT) is not well established.

Objectives: This retrospective cohort study evaluated the incidence of symptomatic pulmonary embolism (PE) after CVC removal using data from the multi-institutional Children's Hospital-Acquired Thrombosis (CHAT) Consortium Registry.

Patients/methods: The CHAT Registry consists of data from children aged 0-21 years with a hospital-acquired venous thromboembolism. Eligible subjects were those with CRT diagnosed <3 days after CVC removal. Subjects were excluded if the CRT was due to a failed CVC insertion. Subjects were divided into three groups: those with CVC removal without anticoagulation, those with CVC removal <48 h after starting anticoagulation, and those with CVC removal ≥48 h after starting anticoagulation.

Results: A total of 687 CRT events from 663 subjects were included. A majority of CRT events were in subjects with peripherally inserted central catheters (62.3%, n = 428). For the 611 CRT events in which the CVC was removed, there was only one case of symptomatic PE (0.16%), which occurred <48 h after initiation of anticoagulation.

Conclusions: While current guidelines suggest anticoagulation before CVC removal in the setting of a CRT to prevent embolization, CVC removal is not associated with symptomatic PE regardless of duration of anticoagulation before CVC removal.
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http://dx.doi.org/10.1111/jth.15548DOI Listing
October 2021

A New Risk Assessment Model for Hospital-Acquired Venous Thromboembolism in Critically Ill Children: A Report From the Children's Hospital-Acquired Thrombosis Consortium.

Pediatr Crit Care Med 2021 Aug 18. Epub 2021 Aug 18.

Division of Hematology/Oncology/Bone Marrow Transplant, Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA. Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, CA. Division of Hematology, CHOC Children's Hospital, Orange, CA. Department of Hematology/Oncology, Children's Hospital Colorado, Aurora, CO. University of Colorado School of Medicine, Aurora, CO. Versiti Blood Research Institute, Milwaukee, WI. Data Coordinating Center, Johns Hopkins All Children's Institute for Clinical and Translational Research, St. Petersburg, FL. Department of Pediatrics, Yale School of Medicine, New Haven, CT. Department of Hematology, Oncology and Blood and Marrow Transplant, Children's Mercy Hospital, Kansas City, MO. Division of Hematology/Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, MA. Harvard Medical School, Boston, MA. Department of Cancer and Blood Disorders, Akron Children's Hospital, Akron, OH. Department of Hematology/Oncology, Children's Hospital of Pittsburgh, Pittsburgh, PA. Indiana Hemophilia and Thrombosis Center, Indianapolis, IN. Department of Medicine and Department of Pathology & Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington, VT. Departments of Oncology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD. Departments of Pediatrics and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

Objectives: To create a risk model for hospital-acquired venous thromboembolism in critically ill children upon admission to an ICU.

Design: Case-control study.

Setting: ICUs from eight children's hospitals throughout the United States.

Subjects: Critically ill children with hospital-acquired venous thromboembolism (cases) 0-21 years old and similar children without hospital-acquired venous thromboembolism (controls) from January 2012 to December 2016. Children with a recent cardiac surgery, asymptomatic venous thromboembolism, or a venous thromboembolism diagnosed before ICU admission were excluded.

Interventions: None.

Measurements And Main Results: The multi-institutional Children's Hospital-Acquired Thrombosis registry was used to identify cases and controls. Multivariable logistic regression was used to determine the association between hospital-acquired venous thromboembolism and putative risk factors present at or within 24 hours of ICU admission to develop the final model. A total of 548 hospital-acquired venous thromboembolism cases (median age, 0.8 yr; interquartile range, 0.1-10.2) and 187 controls (median age, 2.4 yr; interquartile range, 0.2-8.3) were analyzed. In the multivariable model, recent central venous catheter placement (odds ratio, 4.4; 95% CI, 2.7-7.1), immobility (odds ratio 3.6, 95% CI, 2.1-6.2), congenital heart disease (odds ratio 2.9, 95% CI, 1.7-4.7), length of hospital stay prior to ICU admission greater than or equal to 3 days (odds ratio, 2.5; 95% CI, 1.1-5.6), and history of autoimmune/inflammatory condition or current infection (odds ratio, 2.1; 95% CI, 1.2-3.4) were each independently associated with hospital-acquired venous thromboembolism. The risk model had an area under the receiver operating characteristic curve of 0.79 (95% CI, 0.73-0.84).

Conclusions: Using the multicenter Children's Hospital-Acquired Thrombosis registry, we identified five independent risk factors for hospital-acquired venous thromboembolism in critically ill children, deriving a new hospital-acquired venous thromboembolism risk assessment model. A prospective validation study is underway to define a high-risk group for risk-stratified interventional trials investigating the efficacy and safety of prophylactic anticoagulation in critically ill children.
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http://dx.doi.org/10.1097/PCC.0000000000002826DOI Listing
August 2021

Development of a Risk Model for Pediatric Hospital-Acquired Thrombosis: A Report from the Children's Hospital-Acquired Thrombosis Consortium.

J Pediatr 2021 01 10;228:252-259.e1. Epub 2020 Sep 10.

CHOC Children's Hospital, Mission Viejo, CA.

Objective: To identify pertinent clinical variables discernible on the day of hospital admission that can be used to assess risk for hospital-acquired venous thromboembolism (HA-VTE) in children.

Study Design: The Children's Hospital-Acquired Thrombosis Registry is a multi-institutional registry for all hospitalized participants aged 0-21 years diagnosed with a HA-VTE and non-VTE controls. A risk assessment model (RAM) for the development of HA-VTE using demographic and clinical VTE risk factors present at hospital admission was derived using weighted logistic regression and the least absolute shrinkage and selection (Lasso) procedure. The models were internally validated using 5-fold cross-validation. Discrimination and calibration were assessed using area under the receiver operating characteristic curve and Hosmer-Lemeshow goodness of fit, respectively.

Results: Clinical data from 728 cases with HA-VTE and 839 non-VTE controls, admitted between January 2012 and December 2016, were abstracted. Statistically significant RAM elements included age <1 year and 10-22 years, cancer, congenital heart disease, other high-risk conditions (inflammatory/autoimmune disease, blood-related disorder, protein-losing state, total parental nutrition dependence, thrombophilia/personal history of VTE), recent hospitalization, immobility, platelet count >350 K/μL, central venous catheter, recent surgery, steroids, and mechanical ventilation. The area under the receiver operating characteristic curve was 0.78 (95% CI 0.76-0.80).

Conclusions: Once externally validated, this RAM will identify those who are at low-risk as well as the greatest-risk groups of hospitalized children for investigation of prophylactic strategies in future clinical trials.
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http://dx.doi.org/10.1016/j.jpeds.2020.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752847PMC
January 2021

Atypical Outcomes for Hepatitis-associated Acquired Aplastic Anemia: 2 Case Studies and Review of the Literature.

J Pediatr Hematol Oncol 2021 07;43(5):195-199

UPMC Children's Hospital of Pittsburgh.

There is little data specifically dedicated to the long-term outcomes of the hepatitis-associated variant of aplastic anemia (HAAA). A majority of patients with nonsevere (moderate) aplastic anemia progress to severe aplastic anemia, and severe aplastic anemia typically results in death if left untreated. We present 2 unique cases of HAAA that contribute to our knowledge of the natural history of this disease variant. One patient had moderate HAAA that never progressed to severe disease. The second patient had severe HAAA that spontaneously resolved without treatment. The rare possibility of moderate HAAA failing to progress to fulfill severe criteria, or of severe HAAA spontaneously improving, may complicate early treatment decisions for some patients.
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http://dx.doi.org/10.1097/MPH.0000000000001916DOI Listing
July 2021

Generation of twenty four induced pluripotent stem cell lines from twenty four members of the Lothian Birth Cohort 1936.

Stem Cell Res 2020 07 20;46:101851. Epub 2020 May 20.

iPSC Core, The David Janet Polak Foundation Stem Cell Core Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Cedars-Sinai Biomanufacturing Center, West Hollywood, CA 90069, USA; Board of Governors-Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. Electronic address:

Cognitive decline is among the most feared aspects of ageing. We have generated induced pluripotent stem cells (iPSCs) from 24 people from the Lothian Birth Cohort 1936, whose cognitive ability was tested in childhood and in older age. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using non-integrating oriP/EBNA1 backbone plasmids expressing six iPSC reprogramming factors (OCT3/4 (POU5F1), SOX2, KLF4, L-Myc, shp53, Lin28, SV40LT). All lines demonstrated STR matched karyotype and pluripotency was validated by multiple methods. These iPSC lines are a valuable resource to study molecular mechanisms underlying individual differences in cognitive ageing and resilience to age-related neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.scr.2020.101851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347008PMC
July 2020

Unsuspected Lyme disease presenting in refractory haemophilic haemarthrosis.

Haemophilia 2019 Sep 29;25(5):e331-e333. Epub 2019 Jul 29.

Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.

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http://dx.doi.org/10.1111/hae.13821DOI Listing
September 2019

Conditional Gene Knockout in Human Cells with Inducible CRISPR/Cas9.

Methods Mol Biol 2019 ;1961:185-209

Wellcome Trust-MRC Stem Cell Institute, Anne McLaren Laboratory, University of Cambridge, Cambridge, UK.

The advent of the easily programmable and efficient CRISPR/Cas9 nuclease system has revolutionized genetic engineering. While conventional gene knockout experiments using CRISPR/Cas9 are very valuable, these are not well suited to study stage-specific gene function in dynamic situations such as development or disease. Here we describe a CRISPR/Cas9-based OPTimized inducible gene KnockOut method (OPTiKO) for conditional loss-of-function studies in human cells. This approach relies on an improved tetracycline-inducible system for conditional expression of single guide RNAs (sgRNAs) that drive Cas9 activity. In order to ensure homogeneous and stable expression, the necessary transgenes are expressed following rapid and efficient single-step genetic engineering of the AAVS1 genomic safe harbor. When implemented in human pluripotent stem cells (hPSCs), the approach can be then efficiently applied to virtually any hPSC-derived human cell type at various stages of development or disease.
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http://dx.doi.org/10.1007/978-1-4939-9170-9_12DOI Listing
July 2019

Improving the Evaluation and Management of Abnormal Uterine Bleeding in Female Adolescents Presenting for Emergency Care.

J Pediatr Adolesc Gynecol 2019 Apr 17;32(2):128-134. Epub 2018 Nov 17.

Emergency Medicine Division, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.

Study Objective: We sought to improve emergency care for adolescents with abnormal uterine bleeding (AUB) by developing a clinical effectiveness guideline (CEG) and assessing its effect on quality of care.

Design, Setting, Participants, And Interventions: A stakeholder engagement group designed a CEG algorithm for emergency AUB management. Pediatric residents received CEG training and their knowledge and attitudes were assessed using pre- and post intervention surveys. International Classification of Diseases ninth and 10th revision codes identified electronic health record data for patients who presented to the pediatric emergency department for AUB 6 months before and after CEG implementation. A weighted, 20-point scoring system consisting of prioritized aspects of history, laboratory studies, and management was developed to quantify the quality of care provided.

Main Outcome Measures: Descriptive statistics, χ test, Wilcoxon rank sum test, and a run chart were used for analysis.

Results: Pediatric residents reported higher confidence and knowledge scores post CEG implementation. Of the 91 patients identified, 62 met inclusion criteria. Median score was 14 ± 7 before CEG implementation and 15.5 ± 6 after. The Wilcoxon rank sum test showed a difference in AUB evaluation and management scores (P = .09) after implementation of the CEG. Run chart data showed no shifts or trends (overall median score, 14 points). Pre- and post implementation, points were deducted most frequently for not assessing personal/family clotting disorder history. The largest improvements in care were with appropriate medication dosing and disposition.

Conclusion: We designed a CEG and educational intervention for AUB management in a pediatric emergency department. These findings suggest our CEG might be an effective tool to improve emergency AUB care for adolescents and could increase trainees' confidence in managing this condition, although additional cycles are needed.
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http://dx.doi.org/10.1016/j.jpag.2018.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091628PMC
April 2019

Response to treatment and adverse events associated with use of recombinant activated factor VII in children: a retrospective cohort study.

Ther Adv Drug Saf 2017 Feb 20;8(2):51-59. Epub 2016 Oct 20.

Professor and Vice-Chair for Clinical Affairs, Department of Pediatrics, Division of Hematology/Oncology/BMT, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Background: Recombinant activated factor VII (rFVIIa) is United States (US) Food and Drug Administration (FDA)-approved for patients with hemophilia with inhibitors or congenital factor VII deficiency. Initial reports of off-label use highlighted its efficacy, though newer reports have not repeated these findings. In both types of publication, though, secondary thromboses have been seen in adult patients. The data in children are less clear.

Methods: This study analyzed all rFVIIa use at a large children's hospital for characteristics and outcomes. Recipients of rFVIIa were identified retrospectively the electronic medical record. Data on patient diagnosis, lab data, other treatments, adverse events, and outcomes were collected.

Results: Over 33 months, 66 patient episodes were treated with a total of 606 doses (median = 2). The most common indication (36.4%) was gastrointestinal bleeding (24/66 patients). Only one patient received a dose for an approved labeled indication. For control of bleeding, 33.3% of courses were unsuccessful (19/57). Bleeding from multiple sites was associated with treatment failure. In 16.7% of patients (11/66), unexpected adverse thromboses developed within 1 week of completing a course of rFVIIa. Thromboses in both intra- and extra-corporeal sites were included if they compromised patient care.

Conclusions: In the majority of cases reviewed, rFVIIa was successful in stopping or slowing serious bleeding episodes. It was least effective when a patient had diffuse bleeding at the time of administration. The thrombosis rate of 16.7% was higher than expected, though causality cannot be declared. Further investigation is needed to determine the risk-benefit ratio in children.
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http://dx.doi.org/10.1177/2042098616673991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5315224PMC
February 2017

Venous thromboembolism in pediatric trauma patients: Ten-year experience and long-term follow-up in a tertiary care center.

Pediatr Blood Cancer 2017 Aug 9;64(8). Epub 2017 Jan 9.

Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.

Background: Pediatric trauma patients are at high risk for development of venous thromboembolism (VTE). Our objective is to describe incidence, risk factors, and timing of development of VTE, anticoagulation complications, and long-term VTE outcomes in a critically injured pediatric population.

Procedure: We did a retrospective review of pediatric (0-17 years) trauma admissions to intensive care unit from 2005 to 2014. Our center employs VTE screening and prevention protocols for high-risk patients based on hypercoagulable history, age, injuries, and medical interventions. We collected demographics, VTE prevention measures, VTE incidence, therapeutic anticoagulant use, and outcomes including postthrombotic syndrome (PTS) and clot resolution. Analysis included Wilcoxon rank-sum, Fisher exact, and logistic regression modeling.

Results: Seven hundred fifty-three subjects were analyzed. No patients on chemical prophylaxis (21/753) developed VTE. Overall incidence of deep vein thrombosis (DVT) was 8.9%; pulmonary embolism (PE) was 0%. Time to diagnosis was median (interquartile range [IQR]) 10.5 (6.5-14.5) days, with 63% of clots being symptomatic. Risk factors for VTE development included severe traumatic brain injury (TBI), acute traumatic coagulopathy (defined by elevated admission international normalized ratio), age less than or equal to 3 or age 13 years or more, injury severity, and child abuse mechanism. At a median (IQR) follow-up of 13 (6-19) months, 52.1% had persistent clot and 15.8% had PTS. Therapeutic anticoagulation was not associated with clot resolution or prevention of PTS.

Conclusion: TBI therapy is closely linked to the development of DVT. Coagulopathy on admission is associated with hypercoagulability in the postinjury period, suggesting a patient phenotype with systemic coagulation dysregulation. Treatment was not associated with improved VTE outcomes, suggesting that pediatric protocols should emphasize VTE prevention and prophylaxis strategies.
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http://dx.doi.org/10.1002/pbc.26415DOI Listing
August 2017

Optimized inducible shRNA and CRISPR/Cas9 platforms for in vitro studies of human development using hPSCs.

Development 2016 12;143(23):4405-4418

Wellcome Trust-MRC Stem Cell Institute, Anne McLaren Laboratory, University of Cambridge, Cambridge, CB2 0SZ, UK

Inducible loss of gene function experiments are necessary to uncover mechanisms underlying development, physiology and disease. However, current methods are complex, lack robustness and do not work in multiple cell types. Here we address these limitations by developing single-step optimized inducible gene knockdown or knockout (sOPTiKD or sOPTiKO) platforms. These are based on genetic engineering of human genomic safe harbors combined with an improved tetracycline-inducible system and CRISPR/Cas9 technology. We exemplify the efficacy of these methods in human pluripotent stem cells (hPSCs), and show that generation of sOPTiKD/KO hPSCs is simple, rapid and allows tightly controlled individual or multiplexed gene knockdown or knockout in hPSCs and in a wide variety of differentiated cells. Finally, we illustrate the general applicability of this approach by investigating the function of transcription factors (OCT4 and T), cell cycle regulators (cyclin D family members) and epigenetic modifiers (DPY30). Overall, sOPTiKD and sOPTiKO provide a unique opportunity for functional analyses in multiple cell types relevant for the study of human development.
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http://dx.doi.org/10.1242/dev.138081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5201041PMC
December 2016

A Comparison of Extremity Thrombosis Rates in Adolescent and Young Adult Versus Younger Pediatric Oncology Patients at a Children's Hospital.

J Adolesc Young Adult Oncol 2017 Mar 25;6(1):62-66. Epub 2016 Oct 25.

2 Department of Oncology, Johns Hopkins School of Medicine, Johns Hopkins All Children's Hospital , St. Petersburg, Florida.

Purpose: To examine whether the rates of thrombosis in children (≤14 years of age) and adolescent/young adult (AYA) patients (15-22 years of age) with cancer is different.

Methods: We retrospectively studied the rates of thrombosis in children and AYA patients at the Children's Hospital of Pittsburgh during the years 2002-2010, using the tumor registry database. This list was then divided into two groups based on age at diagnosis. A review of ICD-9 codes from hospital billing records was then performed to identify patients who carried diagnoses of cancer (140.x-239.x) and venous thrombosis of the extremities/vena cavae (453.x) simultaneously. This list was confirmed by electronic medical record review. Proportions, comparisons, and descriptive statistics were then performed.

Results: One thousand three hundred nine total patients were identified; 274 patients fit into the AYA age category (mean age 17.3 years) and 1036 patients were in the child group (mean age 6.5 years). Overall, 30 patients (2.29%) had thrombosis: 4.76% of the AYA patients (13/273) and 1.64% of the child group (17/1036). The difference in these proportions had a p-value = 0.004.

Conclusions: This study suggests that the risk of extremity deep vein thrombosis is higher in the AYA subset of oncology patients than in the patients who are 14 years or younger. Prospective studies to elucidate the true rate of thrombosis, as well as to study the benefit of prophylactic anticoagulation in the AYA population, should be undertaken.
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http://dx.doi.org/10.1089/jayao.2016.0044DOI Listing
March 2017

Portomesenteric Venous Thrombosis in Previously Healthy Adolescents Presenting With Subacute Abdominal Pain.

Clin Pediatr (Phila) 2016 Sep 18;55(10):975-8. Epub 2015 Nov 18.

Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

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http://dx.doi.org/10.1177/0009922815616247DOI Listing
September 2016

Three cost-utility analyses of screening for intracranial hemorrhage in neonates with hemophilia.

J Pediatr Hematol Oncol 2014 Aug;36(6):474-9

*Department of Pediatrics, Division of Hematology/Oncology, Children's Hospital of Pittsburgh of UPMC ‡Section of Decision Sciences and Clinical Decisions Modeling, Department of Medicine, University of Pittsburgh, Pittsburgh, PA †Department of Pediatrics, Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN.

Background: Intracranial hemorrhage (ICH) in the newborn period is a potential cause of serious morbidity and mortality in individuals with hemophilia. The incidence of ICH is estimated to be 2% to 4%; however, depending on the mode of delivery, it may be considerably higher. Considering the varying sensitivities and costs of various imaging modalities, there remains controversy surrounding universal cranial imaging. Cost-utility analysis is the ideal tool to display the consequences of a decision made.

Methods: We constructed a decision tree to evaluate the direct and indirect costs, possible outcomes, and probabilities of ICH in neonates with hemophilia. We created 3 decision analysis models to evaluate the cost-utility of different screening modalities for ICH: ultrasound, computed tomography, and magnetic resonance imaging. Within each model, 3 different strategies were compared: screen all neonates; screen only neonates born by instrumented delivery; and not screen any neonates. A societal perspective was used for all models. The base case models were later reanalyzed in sensitivity analysis to account for uncertainties.

Results: Total costs for screening all neonates, screening only neonates born by instrumented delivery, and not screening any neonates were $9501, $9297, and $9347, respectively, for US, and $9761, $9351, and $9353, respectively, for CT. Screening instrumented deliveries using MRI had an incremental cost-effectiveness ratio of $12,440.

Conclusions: Screening newborns born by an instrumented delivery appears to be the most cost-effective strategy irrespective of the imaging modality. Subsequent studies will require a longer time frame to factor in possible late effects of radiation, anesthesia, and the high cost of factor replacement and hospital admission.
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http://dx.doi.org/10.1097/MPH.0000000000000174DOI Listing
August 2014

The zebrafish reference genome sequence and its relationship to the human genome.

Nature 2013 Apr 17;496(7446):498-503. Epub 2013 Apr 17.

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.
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http://dx.doi.org/10.1038/nature12111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703927PMC
April 2013

Meta-analyzing the link between MTHFR C677T genotype and susceptibility to childhood ALL.

Pediatr Blood Cancer 2012 Apr 16;58(4):483-4. Epub 2011 Dec 16.

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http://dx.doi.org/10.1002/pbc.23223DOI Listing
April 2012

A resource of vectors and ES cells for targeted deletion of microRNAs in mice.

Nat Biotechnol 2011 Aug 7;29(9):840-5. Epub 2011 Aug 7.

The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.

The 21-23 nucleotide, single-stranded RNAs classified as microRNAs (miRNA) perform fundamental roles in diverse cellular and developmental processes. In contrast to the situation for protein-coding genes, no public resource of miRNA mouse mutant alleles exists. Here we describe a collection of 428 miRNA targeting vectors covering 476 of the miRNA genes annotated in the miRBase registry. Using these vectors, we generated a library of highly germline-transmissible C57BL/6N mouse embryonic stem (ES) cell clones harboring targeted deletions for 392 miRNA genes. For most of these targeted clones, chimerism and germline transmission can be scored through a coat color marker. The targeted alleles have been designed to be adaptable research tools that can be efficiently altered by recombinase-mediated cassette exchange to create reporter, conditional and other allelic variants. This miRNA knockout (mirKO) resource can be searched electronically and is available from ES cell repositories for distribution to the scientific community.
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http://dx.doi.org/10.1038/nbt.1929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242032PMC
August 2011

A cost-effectiveness analysis of coagulation testing prior to tonsillectomy and adenoidectomy in children.

Pediatr Blood Cancer 2010 Dec;55(6):1153-9

Division of Hematology/Oncology/BMT, Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15224, USA.

Background: The American Society of Pediatric Otolaryngology recommends pre-operative coagulation testing only when indicated by history or physical exam. Nevertheless, many surgeons test all children scheduled for tonsillectomy and/or adenoidectomy (T&A). Studies of pre-operative screening have had conflicting results. A decision analysis model was constructed to address the costs and health outcome states of pre-operative screening strategies in children.

Procedure: A 14-day Markov model evaluated three strategies: (1) test all children for coagulation disorders; (2) test only those children with a pertinent history; and (3) perform no pre-operative testing. A literature search and a review of national databases estimated probabilities, costs, and utility data. Parameters then were varied widely in sensitivity analyses. Using a societal perspective and a cycle length of 1 day, we compared the strategies based on total costs and quality-adjusted life years (QALYs).

Results: Total costs for the strategies were $3,200 for testing all children, $3,083 for testing only those with a history finding, and $3,077 for not testing. Total utilities were 0.02579, 0.02654, and 0.02659 QALYs, respectively. Cost-effectiveness ratios were most sensitive to variation in the cost of post-operative care and the probability of post-operative bleeding. The strategy of not testing was dominant in all sensitivity analyses.

Conclusions: Our results demonstrate that not performing preoperative testing is the most cost-effective strategy. This was persistent in sensitivity analyses, indicating that the model was robust. These data may be helpful to institutions and organizations to formulate policies regarding pre-operative coagulation for children without previous diagnoses of bleeding disorders.
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http://dx.doi.org/10.1002/pbc.22708DOI Listing
December 2010

Cerebral fat embolism syndrome causing brain death after long-bone fractures and acetazolamide therapy.

Crit Care Resusc 2007 Jun;9(2):184-6

Alfred Hospital, Melbourne, VIC, Australia.

A 19-year-old woman with multiple fractures and mild brain injury developed severe cerebral fat embolism syndrome after "damage control" orthopaedic surgery. Acetazolamide therapy to manage ocular trauma, in association with hyperchloraemia, caused a profound metabolic acidosis with appropriate compensatory hypocapnia. During ventilator weaning, unexpected brainstem coning followed increased sedation and brief normalisation of arterial carbon dioxide concentration. Autopsy found severe cerebral fat embolism and brain oedema. In patients with multiple trauma, cerebral fat embolism syndrome is difficult to diagnose, and may be more common after delayed fixation of long-bone fractures. Acetazolamide should be used with caution, as sudden restoration of normocapnia during compensated metabolic acidosis in patients with raised intracranial pressure may precipitate coning.
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June 2007

Factors predicting cervical collar-related decubitus ulceration in major trauma patients.

Spine (Phila Pa 1976) 2007 Feb;32(4):423-8

National Trauma Research Institute, Alfred Hospital, Melbourne, Australia.

Study Design: Retrospective medical record and electronic database audit to ascertain the incidence and predictors of cervical collar-related decubitus ulceration (CRU).

Objective: To determine the incidence and risk factors associated with the development of CRU in major trauma patients immobilized in Philadelphia cervical collars.

Summary Of Background Data: Cervical spine immobilization requires the utilization of a cervical collar before spinal clearance, which may be complicated by CRU and increased morbidity.

Methods: From a trauma registry database at a level 1 trauma center, 299 major trauma patients admitted over a 6-month period were identified. Predictors of CRU were retrospectively examined and assessed for relative importance using medical records and prospective infection control and radiology databases.

Results: Clinically significant predictors of CRU were ICU admission (P = 0.007), mechanical ventilation (P = 0.005), the necessity for cervical MRI (P < or = 0.001), and time to cervical spine clearance (P < or = 0.001). Time to cervical spine clearance was the major indicator, such that the risk of CRU increased by 66% for every 1 day increase in cervical collar time.

Conclusion: In major trauma patients at a level 1 trauma center, the risk of CRU development increased significantly for every day of Philadelphia cervical collar time. Associated increased morbidity may be reduced by measures aimed at earlier cervical spine clearance.
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http://dx.doi.org/10.1097/01.brs.0000255096.52871.4eDOI Listing
February 2007

Inaccurate information about lyme disease on the internet.

Pediatr Infect Dis J 2004 Dec;23(12):1105-8

University of Connecticut Health Center, Farmington, CT, USA.

Objective: Patients and families searching the Internet about Lyme disease may find conflicting information. Our purpose was to review the accuracy of information on Lyme disease easily available on the Internet.

Methods: We used 15 search engines to find general information about Lyme disease. We found 251 Lyme disease websites, which we reviewed. Of these 251 websites, 19 gave general Lyme disease information and were analyzed. We evaluated the accuracy of information concerning 8 Lyme disease topics.

Results: Ten of the 19 websites gave accurate information and 9 of the 19 websites provided inaccurate information. There were 8 websites with the word "Lyme" in the domain name, and 7 of the 8 sites gave inaccurate information. There were 2 ".gov" websites, and both gave accurate information.

Conclusions: Patients and families searching the Internet for medical information about Lyme disease may encounter inaccurate information.
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December 2004
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