65 results on '"Clarke JE"'
Search Results
2. A MULTI-FACETED ACOUSTIC GROUND-TRUTHING EXPERIMENT IN THE BAY OF FUNDY
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MAYER, LA, primary, HUGHES CLARKE, JE, additional, and WELLS, D, additional
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- 2024
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3. Retinal ganglion cell-specific genetic regulation in primary open-angle glaucoma.
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Daniszewski, M, Senabouth, A, Liang, HH, Han, X, Lidgerwood, GE, Hernández, D, Sivakumaran, P, Clarke, JE, Lim, SY, Lees, JG, Rooney, L, Gulluyan, L, Souzeau, E, Graham, SL, Chan, C-L, Nguyen, U, Farbehi, N, Gnanasambandapillai, V, McCloy, RA, Clarke, L, Kearns, LS, Mackey, DA, Craig, JE, MacGregor, S, Powell, JE, Pébay, A, Hewitt, AW, Daniszewski, M, Senabouth, A, Liang, HH, Han, X, Lidgerwood, GE, Hernández, D, Sivakumaran, P, Clarke, JE, Lim, SY, Lees, JG, Rooney, L, Gulluyan, L, Souzeau, E, Graham, SL, Chan, C-L, Nguyen, U, Farbehi, N, Gnanasambandapillai, V, McCloy, RA, Clarke, L, Kearns, LS, Mackey, DA, Craig, JE, MacGregor, S, Powell, JE, Pébay, A, and Hewitt, AW
- Abstract
To assess the transcriptomic profile of disease-specific cell populations, fibroblasts from patients with primary open-angle glaucoma (POAG) were reprogrammed into induced pluripotent stem cells (iPSCs) before being differentiated into retinal organoids and compared with those from healthy individuals. We performed single-cell RNA sequencing of a total of 247,520 cells and identified cluster-specific molecular signatures. Comparing the gene expression profile between cases and controls, we identified novel genetic associations for this blinding disease. Expression quantitative trait mapping identified a total of 4,443 significant loci across all cell types, 312 of which are specific to the retinal ganglion cell subpopulations, which ultimately degenerate in POAG. Transcriptome-wide association analysis identified genes at loci previously associated with POAG, and analysis, conditional on disease status, implicated 97 statistically significant retinal ganglion cell-specific expression quantitative trait loci. This work highlights the power of large-scale iPSC studies to uncover context-specific profiles for a genetically complex disease.
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- 2022
4. Retinal ganglion cell-specific genetic regulation in primary open angle glaucoma
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Craig Jee, Gnanasambandapillai, Stuart MacGregor, David A. Mackey, Damián Hernández, Xikun Han, Alex W. Hewitt, Uyen Nguyen, Joseph E. Powell, Lisa S. Kearns, Helena Liang, Nona Farbehi, Shiang Y. Lim, Clarke Je, Chia-Ling Chan, Grace E. Lidgerwood, Alice Pébay, Stuart L. Graham, Lerna Gulluyan, Maciej S. Daniszewski, Louise A. Rooney, Anne Senabouth, Emmanuelle Souzeau, Jarmon G Lees, Linda Clarke, Priyadharshini Sivakumaran, and Rachael A. McCloy
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Genetics ,Cell type ,Retinal ,Quantitative trait locus ,Biology ,Retinal ganglion ,chemistry.chemical_compound ,medicine.anatomical_structure ,Retinal ganglion cell ,chemistry ,Expression quantitative trait loci ,medicine ,Induced pluripotent stem cell ,Genetic association - Abstract
To assess the transcriptomic profile of disease-specific cell populations, fibroblasts from patients with primary open-angle glaucoma (POAG) were reprogrammed into induced pluripotent stem cells (iPSCs) before being differentiated into retinal organoids and compared to those from healthy individuals. We performed single-cell RNA-sequencing of a total of 330,569 cells and identified cluster-specific molecular signatures. Comparing the gene expression profile between cases and controls, we identified novel genetic associations for this blinding disease. Expression quantitative trait mapping identified a total of 2,235 significant loci across all cell types, 58 of which are specific to the retinal ganglion cell subpopulations, which ultimately degenerate in POAG. Transcriptome-wide association analysis identified genes at loci previously associated with POAG, and analysis, conditional on disease status, implicated 54 statistically significant retinal ganglion cell-specific expression quantitative trait loci. This work highlights the power of large-scale iPSC studies to uncover context-specific profiles for a genetically complex disease.
- Published
- 2021
5. THE GEAC EXPERIENCE AT HILLINGDON
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Mr. Clarke, JE
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- 1985
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6. Acoustic detection of organic enrichment in sediments at a salmon farm is confirmed by independent groundtruthing methods
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Wildish, DJ, primary, Hughes-Clarke, JE, additional, Pohle, GW, additional, Hargrave, BT, additional, and Mayer, LM, additional
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- 2004
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7. Medical evacuation and triage of combat casualties in Helmand Province, Afghanistan: October 2010-April 2011.
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Clarke JE, Davis PR, Clarke, Jonathan E, and Davis, Peter R
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Medical evacuation of combat casualties in Operation Enduring Freedom-Afghanistan is achieved primarily by helicopter, because of distances involved as well as ground-based threats. In Helmand Province, evacuation from the point of injury may occur on a variety of helicopter evacuation platforms with disparate levels of attendant medical expertise. Furthermore, triage to a medical treatment facility may involve varying echelons of care before definitive management. Consequently, considerable differences in medical care may be encountered between point of injury and definitive treatment. We discuss the role of helicopter-based medical evacuation in Helmand, Afghanistan, as well as triage and timelines to the most appropriate medical facilities. Based on our experience and available evidence, we have made recommendations to regional commanders which favor the utilization of prehospital critical care teams aboard helicopter-based evacuation platforms and direct triage to the highest echelon of care available when feasible. [ABSTRACT FROM AUTHOR]
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- 2012
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8. Trypanosome infections in the mouthparts ofGlossina morsitansWestw.: a correlation between extent of labral infection and invasion of the hypopharynx
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Clarke Je
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Trypanosoma ,Tsetse Flies ,Research ,030231 tropical medicine ,Glossina morsitans ,Biology ,biology.organism_classification ,medicine.disease ,Virology ,Arthropod mouthparts ,Hypopharynx ,03 medical and health sciences ,Trypanosomiasis, African ,0302 clinical medicine ,Infectious Diseases ,030225 pediatrics ,medicine ,Animals ,Parasitology ,Trypanosomiasis - Published
- 1965
9. THE GEAC EXPERIENCE AT HILLINGDON
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Clarke, JE, primary
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- 1985
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10. Health effects of the Federal Bureau of Prisons tobacco ban
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Martin Stephen A, Celli Bartolome R, DiFranza Joseph R, Krinzman Stephen J, Clarke Jennifer G, Beam Herbert, Howard Sandra, Foster Melissa, and Goldberg Robert J
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Pulmonary disease ,Chronic Obstructive Pulmonary Disease ,Asthma ,Pathophysiology ,Biomarkers ,Pulmonary function tests ,Tobacco ,Nicotine ,Addiction ,Health services ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Tobacco smoking remains the leading cause of preventable death in America, claiming 450,000 lives annually. Chronic Obstructive Pulmonary Disease, caused by smoking in the vast majority of cases, became the third leading cause of death in the U.S. in 2008. The burden of asthma, often exacerbated by tobacco exposure, has widespread clinical and public health impact. Despite this considerable harm, we know relatively little about the natural history of lung disease and respiratory impairment in adults, especially after smoking cessation. Methods/Design Our paper describes the design and rationale for using the 2004 Federal Bureau of Prisons tobacco ban to obtain insights into the natural history of respiratory diseases in adult men and women of different races/ethnicities who are imprisoned in federal medical facilities. We have developed a longitudinal study of new prison arrivals, with data to be collected from each participant over the course of several years, through the use of standardized questionnaires, medical chart reviews, lung function tests, six-minute walk tests, and stored serum for the analysis of present and future biomarkers. Our endpoints include illness exacerbations, medication and health services utilization, lung function, serum biomarkers, and participants’ experience with their health and nicotine addiction. Discussion We believe the proposed longitudinal study will make a substantial contribution to the understanding and treatment of respiratory disease and tobacco addiction.
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- 2012
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11. Motivational Interviewing with computer assistance as an intervention to empower women to make contraceptive choices while incarcerated: study protocol for randomized controlled trial
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Clarke Jennifer, Gold Melanie A, Simon Rachel E, Roberts Mary B, and Stein LAR
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Medicine (General) ,R5-920 - Abstract
Abstract Background Unplanned pregnancies and sexually transmitted infections (STIs) are important and costly public health problems in the United States resulting from unprotected sexual intercourse. Risk factors for unplanned pregnancies and STIs (poverty, low educational attainment, homelessness, substance abuse, lack of health insurance, history of an abusive environment, and practice of commercial sex work) are especially high among women with a history of incarceration. Project CARE (Contraceptive Awareness and Reproductive Education) is designed to evaluate an innovative intervention, Motivational Interviewing with Computer Assistance (MICA), aimed at enhancing contraceptive initiation and maintenance among incarcerated women who do not want a pregnancy within the next year and who are anticipated to be released back to the community. This study aims to: (1) increase the initiation of highly effective contraceptives while incarcerated; (2) increase the continuation of highly effective contraceptive use at 3, 6, 9, and 12 months after release; and (3) decrease unsafe sexual activity. Methods/Design This randomized controlled trial will recruit 400 women from the Rhode Island Department of Corrections (RI DOC) women’s jail at risk for an unplanned pregnancy (that is, sexually active with men and not planning/wanting to become pregnant in the next year). They will be randomized to two interventions: a control group who receive two educational videos (on contraception, STIs, and pre-conception counseling) or a treatment group who receive two sessions of personalized MICA. MICA is based on the principles of the Transtheoretical Model (TTM) and on Motivational Interviewing (MI), an empirically supported counseling technique designed to enhance readiness to change targeted behaviors. Women will be followed at 3, 6, 9, and 12 months post release and assessed for STIs, pregnancy, and reported condom use. Discussion Results from this study are expected to enhance our understanding of the efficacy of MICA to enhance contraceptive initiation and maintenance and reduce sexual risk-taking behaviors among incarcerated women who have re-entered the community. Trial registration NCT01132950
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- 2012
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12. Non-peptidergic small diameter primary afferents expressing VGluT2 project to lamina I of mouse spinal dorsal horn
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Clarke Jennifer N, Anderson Rebecca L, Haberberger Rainer V, and Gibbins Ian L
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nociceptors ,primary afferent neurons ,VGluT2 ,CGRP ,microdomain ,spinal dorsal horn ,Pathology ,RB1-214 - Abstract
Abstract Background Unmyelinated primary afferent nociceptors are commonly classified into two main functional types: those expressing neuropeptides, and non-peptidergic fibers that bind the lectin IB4. However, many small diameter primary afferent neurons neither contain any known neuropeptides nor bind IB4. Most express high levels of vesicular glutamate transporter 2 (VGluT2) and are assumed to be glutamatergic nociceptors but their terminations within the spinal cord are unknown. We used in vitro anterograde axonal tracing with Neurobiotin to identify the central projections of these putative glutamatergic nociceptors. We also quantitatively characterised the spatial arrangement of these terminals with respect to those that expressed the neuropeptide, calcitonin gene-related peptide (CGRP). Results Neurobiotin-labeled VGluT2-immunoreactive (IR) terminals were restricted to lamina I, with a medial-to-lateral distribution similar to CGRP-IR terminals. Most VGluT2-IR terminals in lateral lamina I were not labeled by Neurobiotin implying that they arose mainly from central neurons. 38 ± 4% of Neurobiotin-labeled VGluT2-IR terminals contained CGRP-IR. Conversely, only 17 ± 4% of Neurobiotin-labeled CGRP-IR terminals expressed detectable VGluT2-IR. Neurobiotin-labeled VGluT2-IR or CGRP-IR terminals often aggregated into small clusters or microdomains partially surrounding intrinsic lamina I neurons. Conclusions The central terminals of primary afferents which express high levels of VGluT2-IR but not CGRP-IR terminate mainly in lamina I. The spatial arrangement of VGluT2-IR and CGRP-IR terminals suggest that lamina I neurons receive convergent inputs from presumptive nociceptors that are primarily glutamatergic or peptidergic. This reveals a previously unrecognized level of organization in lamina I consistent with the presence of multiple nociceptive processing pathways.
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- 2011
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13. Working Inside for Smoking Elimination (Project W.I.S.E.) study design and rationale to prevent return to smoking after release from a smoke free prison
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Mello Jennifer, Lopes Cheryl E, Stein LAR, Martin Rosemarie A, Clarke Jennifer G, Friedmann Peter, and Bock Beth
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Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Incarcerated individuals suffer disproportionately from the health effects of tobacco smoking due to the high smoking prevalence in this population. In addition there is an over-representation of ethnic and racial minorities, impoverished individuals, and those with mental health and drug addictions in prisons. Increasingly, prisons across the U.S. are becoming smoke free. However, relapse to smoking is common upon release from prison, approaching 90% within a few weeks. No evidence based treatments currently exist to assist individuals to remain abstinent after a period of prolonged, forced abstinence. Methods/Design This paper describes the design and rationale of a randomized clinical trial to enhance smoking abstinence rates among individuals following release from a tobacco free prison. The intervention is six weekly sessions of motivational interviewing and cognitive behavioral therapy initiated approximately six weeks prior to release from prison. The control group views six time matched videos weekly starting about six weeks prior to release. Assessments take place in-person 3 weeks after release and then for non-smokers every 3 months up to 12 months. Smoking status is confirmed by urine cotinine. Discussion Effective interventions are greatly needed to assist these individuals to remain smoke free and reduce health disparities among this socially and economically challenged group. Trial Registration NCT01122589
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- 2011
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14. Mitochondrial genome evolution in fire ants (Hymenoptera: Formicidae)
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Shoemaker DeWayne, Clarke Jessica, and Gotzek Dietrich
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Evolution ,QH359-425 - Abstract
Abstract Background Complete mitochondrial genome sequences have become important tools for the study of genome architecture, phylogeny, and molecular evolution. Despite the rapid increase in available mitogenomes, the taxonomic sampling often poorly reflects phylogenetic diversity and is often also biased to represent deeper (family-level) evolutionary relationships. Results We present the first fully sequenced ant (Hymenoptera: Formicidae) mitochondrial genomes. We sampled four mitogenomes from three species of fire ants, genus Solenopsis, which represent various evolutionary depths. Overall, ant mitogenomes appear to be typical of hymenopteran mitogenomes, displaying a general A+T-bias. The Solenopsis mitogenomes are slightly more compact than other hymentoperan mitogenomes (~15.5 kb), retaining all protein coding genes, ribosomal, and transfer RNAs. We also present evidence of recombination between the mitogenomes of the two conspecific Solenopsis mitogenomes. Finally, we discuss potential ways to improve the estimation of phylogenies using complete mitochondrial genome sequences. Conclusions The ant mitogenome presents an important addition to the continued efforts in studying hymenopteran mitogenome architecture, evolution, and phylogenetics. We provide further evidence that the sampling across many taxonomic levels (including conspecifics and congeners) is useful and important to gain detailed insights into mitogenome evolution. We also discuss ways that may help improve the use of mitogenomes in phylogenetic analyses by accounting for non-stationary and non-homogeneous evolution among branches.
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- 2010
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15. Long-term survival of a woman with well differentiated papillary mesothelioma of the peritoneum: a case report and review of the literature
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Helft Paul and Clarke Jeffrey M
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Medicine - Abstract
Abstract Introduction Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare subtype of epitheloid mesothelioma, which is usually seen in young women. WDPMP is generally considered of low malignant potential, however the long-term nature of the tumor remains poorly defined. Case presentation We describe the long-term follow-up of a 60-year-old woman of West African descent who has survived 24 years with WDPMP after receiving extensive local and systemic adjuvant chemotherapy. Her clinical course has included three exploratory laparotomies with intraperitoneal and intravenous chemotherapy over two decades. Her course was complicated by anthracycline-induced cardiomyopathy, for which she underwent an orthotopic heart transplant. Our patient is alive with stable radiological evidence of peritoneal disease, and continues to suffer from chronic abdominal pain. Conclusion No consensus exists regarding optimal treatment strategies for WDPMP. However, given the low malignant potential of the tumor, careful consideration should be made before proceeding with aggressive interventions. Further, long-term follow-up reports are required to fully characterize this tumor.
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- 2010
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16. Arterial blood gas estimations in the management of Ludwig's angina
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Clarke, JE
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- 1981
17. MDU Report' and 'What is Informed Consent?'
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Clarke, JE
- Published
- 1989
18. Revolutionizing Intracranial Hemorrhage Diagnosis: A Retrospective Analytical Study of Viz.ai ICH for Enhanced Diagnostic Accuracy.
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Roshan MP, Al-Shaikhli SA, Linfante I, Antony TT, Clarke JE, Noman R, Lamy C, Britton S, Belnap SC, Abrams K, and Sidani C
- Abstract
Introduction Artificial intelligence (AI) alerts the radiologist to the presence of intracranial hemorrhage (ICH) as fast as 1-2 minutes from scan completion, leading to faster diagnosis and treatment. We wanted to validate a new AI application called Viz.ai ICH to improve the diagnosis of suspected ICH. Methods We performed a retrospective analysis of 4,203 consecutive non-contrast brain computed tomography (CT) reports in a single institution between September 1, 2021, and January 31, 2022. The reports were made by neuroradiologists who reviewed each case for the presence of ICH. Reports and identified cases with positive findings for ICH were reviewed. Positive cases were categorized based on subtype, timing, and size/volume. Viz.ai ICH output was reviewed for positive cases. This AI model was validated by assessing its performance with Viz.ai ICH as the index test compared to the neuroradiologists' interpretation as the gold standard. Results According to neuroradiologists, 9.2% of non-contrast brain CT reports were positive for ICH. The sensitivity of Viz.ai ICH was 85%, specificity was 98%, positive predictive value was 81%, and negative predictive value was 99%. Subgroup analysis was performed based on intraparenchymal, subarachnoid, subdural, and intraventricular subtypes. Sensitivities were 94%, 79%, 83%, and 44%, respectively. Further stratification revealed sensitivity improves with higher acuity and volume/size across subtypes. Conclusion Our analysis indicates that AI can accurately detect ICH's presence, particularly for large-volume/large-size ICH. The paper introduces a novel AI model for detecting ICH. This advancement contributes to the field by revolutionizing ICH detection and improving patient outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board of Baptist Health South Florida issued approval IRBNet ID 1849788-2. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Dr. Kevin Abrams MD declare(s) non-financial support from Viz.ai. Dr. Kevin Abrams is an advisor for Viz.ai. He was involved in study design and manuscript editing. However, he was not involved in the review of images/data analysis. The remainder of authors have nothing to disclose. The remaining authors have no conflict of interest to disclose. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Roshan et al.)
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- 2024
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19. Preparing Radiologists for an Artificial Intelligence-enhanced Future: Tips for Trainees.
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Rouzrokh P, Clarke JE, Hosseiny M, Nikpanah M, and Mokkarala M
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- Humans, Clinical Competence, Education, Medical, Graduate methods, Internship and Residency, Forecasting, Curriculum, Artificial Intelligence, Radiologists education, Radiology education
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- 2024
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20. A New (Digital) Era in Medical Journalism: Leveraging Social Media and Other Online Tools to Increase Reach and Engagement.
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Traylor KS, Bastawrous S, Riedesel EL, Ballard DH, Hochhegger B, Ukeh I, Jaswal S, Agarwal M, Clarke JE, Lakhani DA, Balthazar P, Tomblinson CM, and Bunch PM
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- Humans, Communication, Social Media, Radiology
- Abstract
Social media is a popular communication and marketing tool in modern society, with the power to reach and engage large audiences. Many members of the medical and radiology communities have embraced social media platforms, particularly X (formerly known as Twitter), as an efficient and economic means for performing patient outreach, disseminating research and educational materials, building networks, and promoting diversity. Editors of medical journals with a clear vision and relevant expertise can leverage social media and other digital tools to advance the journal's mission, further their interests, and directly benefit journal authors and readers. For editors, social media offers a means to increase article visibility and downloads, expand awareness of volunteer opportunities, and use metrics and other feedback to inform future initiatives. Authors benefit from broader dissemination of their work, which aids establishment of a national or international reputation. Readers can receive high-quality high-yield content in a digestible format directly on their devices while actively engaging with journal editors and authors in the online community. The authors highlight the multifaceted benefits of social media engagement and digital tool implementation in the context of medical journalism and summarize the activities of the RadioGraphics Social Media and Digital Innovation Team. By enumerating the social media activities of RadioGraphics and describing the underlying rationale for each activity, the authors present a blueprint for other medical journals considering similar initiatives.
© RSNA, 2023.- Published
- 2023
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21. The native ABC-F proteins of Staphylococcus aureus do not contribute to intrinsic resistance against ribosome-targeting antibacterial drugs.
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Galarion LH, Trigwell J, Mohamad M, Nakamoto JA, Clarke JE, Atkinson GC, and O'Neill AJ
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- Humans, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents metabolism, Ribosomes, Microbial Sensitivity Tests, Staphylococcus aureus metabolism, Staphylococcal Infections drug therapy, Staphylococcal Infections microbiology
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- 2023
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22. Assessment of neuromonitoring use and postoperative readmission rates in pediatric Chiari I malformation with syrinx.
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Gilna GP, Clarke JE, Silva M, Saberi RA, Parreco JP, Thorson CM, and McCrea HJ
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- United States, Child, Humans, Female, Adolescent, Male, Patient Readmission, Postoperative Complications etiology, Decompression, Surgical adverse effects, Retrospective Studies, Treatment Outcome, Arnold-Chiari Malformation surgery, Arnold-Chiari Malformation complications, Syringomyelia complications
- Abstract
Introduction: While operative intervention for Chiari malformation type I (CMI) with syringomyelia is well established, there is limited data on outcomes of intraoperative neuromonitoring (IONM). This study sought to explore differences in procedural characteristics and their effects on postoperative readmission rates., Methods: The Nationwide Readmission Database was queried from 2010 to 2014 for patients ≤ 18 years of age with CMI and syringomyelia who underwent cranial decompression or spinal decompression. Demographics, hospital characteristics, and outcomes were analyzed., Results: Over the 5-year period, 2789 patients were identified that underwent operative treatment for CMI with syringomyelia. Mean age was 10 ± 4 years with 55% female. During their index hospitalization 14% of the patients had IONM. Patients receiving IONM had no significant difference in Charleston Comorbidity Index ≥ 1 (16% vs. 15% without, p = 0.774). IONM was more often used in those with private insurance (63% vs. 58% without, p = 0.0004) and less likely in those with Medicaid (29% vs. 37% without, p = 0.004). Patients receiving IONM were more likely to have a postoperative complication (23% vs 17%, p = 0.004) and were more likely to have hospital lengths of stay > 7 days (9% vs. 5% without, p = 0.005). Readmission rates for CMI were 9% within 30 days and 15% within the year. The majority (89%) of readmissions were unplanned. 25% of readmissions were for infection and 27% of readmissions underwent a CMI reoperation. The 30-day readmission rate was higher for those with IONM (12% vs. 8% without, p = 0.010). Median cost for hospitalization was significantly higher for patients with IONM ($26,663 ($16,933-34,397)) vs. those without ($14,577 ($11,538-18,392)), p < 0.001., Conclusion: The use of intraoperative neuromonitoring for operative repair of CMI is associated with higher postoperative complications and readmissions. In addition, there are disparities in its use and increased cost to the healthcare system. Further studies are needed to elucidate the factors underlying this association., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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23. Chiari I malformation management in patients with heritable connective tissue disorders.
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Clarke JE, Reyes JM, Luther E, Govindarajan V, Leuchter JD, Niazi T, Ragheb J, and Wang S
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Background: Chiari malformation type I (CMI) is relatively common neurosurgical condition typically treated with posterior fossa decompression. However, the management of CMI in patients with heritable connective tissue disorders (CTDs), such as Ehlers-Danlos Syndrome, Marfan Syndrome, or Osteogenesis Imperfecta, involves a unique set of perioperative challenges., Objective: This study aims to define the demographic information, comorbidities, and perioperative course of patients with concomitant CMI and CTD., Methods: Patients with CMI admitted for surgical decompression from 2008 to 2015 were captured using the National Inpatient Sample (NIS). Information was collected based on ICD-9 codes. Descriptive and regression analyses were performed in SPSS (version 26)., Results: 38,169 CMI patients, 353 of whom had CTD (0.92%), were identified. CMI patients with CTD were more likely to be female ( p < 0.001) and present during teenage ( p = 0.033) or young adult years ( p < 0.001). They had more chronic issues ( p < 0.001): systemic comorbidities include postural orthostatic tachycardia syndrome, cardiac dysrhythmias, and gastroparesis (all p < 0.001). CNS comorbidities include migraine, tethered spinal cord, and epilepsy (all p < 0.001). They have increased joint instability (both p < 0.001), as well as craniocervical instability (CCI). More posterior cervical fusion surgeries and application of cervical halo devices were seen during the same inpatient stay (both p < 0.001)., Conclusions: Patients with concurrent CTD and CMI were more likely to present with complex Chiari and associated CCI. They were also younger, more often female, and had more systemic, CNS, and joint abnormalities. As such, preoperative recognition of an underlying CTD is imperative to achieve optimal outcomes in this patient population., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)
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- 2023
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24. Siderophore-Linked Ruthenium Catalysts for Targeted Allyl Ester Prodrug Activation within Bacterial Cells.
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Southwell JW, Herman R, Raines DJ, Clarke JE, Böswald I, Dreher T, Gutenthaler SM, Schubert N, Seefeldt J, Metzler-Nolte N, Thomas GH, Wilson KS, and Duhme-Klair AK
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- Animals, Siderophores, Moxifloxacin, Anti-Bacterial Agents pharmacology, Mammals metabolism, Prodrugs pharmacology, Ruthenium
- Abstract
Due to rising resistance, new antibacterial strategies are needed, including methods for targeted antibiotic release. As targeting vectors, chelating molecules called siderophores that are released by bacteria to acquire iron have been investigated for conjugation to antibacterials, leading to the clinically approved drug cefiderocol. The use of small-molecule catalysts for prodrug activation within cells has shown promise in recent years, and here we investigate siderophore-linked ruthenium catalysts for the activation of antibacterial prodrugs within cells. Moxifloxacin-based prodrugs were synthesised, and their catalyst-mediated activation was demonstrated under anaerobic, biologically relevant conditions. In the absence of catalyst, decreased antibacterial activities were observed compared to moxifloxacin versus Escherichia coli K12 (BW25113). A series of siderophore-linked ruthenium catalysts were investigated for prodrug activation, all of which displayed a combinative antibacterial effect with the prodrug, whereas a representative example displayed little toxicity against mammalian cell lines. By employing complementary bacterial growth assays, conjugates containing siderophore units based on catechol and azotochelin were found to be most promising for intracellular prodrug activation., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)
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- 2023
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25. The recognition of structured elements by a conserved groove distant from domains associated with catalysis is an essential determinant of RNase E.
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Clarke JE, Sabharwal K, Kime L, and McDowall KJ
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- Humans, Endoribonucleases metabolism, RNA genetics, RNA metabolism, Catalysis, RNA, Bacterial metabolism, Escherichia coli genetics, Escherichia coli metabolism, Escherichia coli Proteins genetics, Escherichia coli Proteins metabolism
- Abstract
RNase E is an endoribonuclease found in many bacteria, including important human pathogens. Within Escherichia coli, it has been shown to have a major role in both the maturation of all classes of RNA involved in translation and the initiation of mRNA degradation. Thus, knowledge of the major determinants of RNase E cleavage is central to our understanding and manipulation of bacterial gene expression. We show here that the binding of RNase E to structured RNA elements is crucial for the processing of tRNA, can activate catalysis and may be important in mRNA degradation. The recognition of structured elements by RNase E is mediated by a recently discovered groove that is distant from the domains associated with catalysis. The functioning of this groove is shown here to be essential for E. coli cell viability and may represent a key point of evolutionary divergence from the paralogous RNase G family, which we show lack amino acid residues conserved within the RNA-binding groove of members of the RNase E family. Overall, this work provides new insights into the recognition and cleavage of RNA by RNase E and provides further understanding of the basis of RNase E essentiality in E. coli., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2023
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26. Comment on: Identification of a novel tedizolid resistance mutation in rpoB of MRSA after in vitro serial passage.
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Galarion LH, Clarke JE, Schofield H, and O'Neill AJ
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- Serial Passage, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Mutation, Methicillin-Resistant Staphylococcus aureus genetics, Oxazolidinones
- Published
- 2022
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27. Positive predictive value and trends of inferior petrosal sinus sampling (IPSS) in diagnosing cushing disease and ectopic ACTH secretion: A systematic review and meta-analysis.
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Govindarajan V, Lu VM, Clarke JE, Luther EM, Eichberg DG, Morell AA, Shah AH, Starke RM, Kargi AY, Komotar RJ, and Ivan ME
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- Adrenocorticotropic Hormone, Deamino Arginine Vasopressin, Diagnosis, Differential, Humans, Petrosal Sinus Sampling methods, Predictive Value of Tests, ACTH Syndrome, Ectopic diagnosis, Cushing Syndrome diagnosis, Pituitary ACTH Hypersecretion diagnosis
- Abstract
Background: Inferior petrosal sinus sampling (IPSS) offers a means of differentiating between Cushing disease and Cushing syndrome with lower false-positive and false-negative rates relative to traditional techniques. However, consolidated data on efficiency reflecting contemporary use is lacking. We present a comprehensive meta-analysis of IPSS as a means of diagnosing ACTH-cortisol axis derangements via both CRH and desmopressin-stimulated techniques., Methods: Searches of 7 electronic databases from inception to December 2020 were conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. Outcomes were pooled by random-effects meta-analyses of proportions where possible. We performed a meta-analysis of sixty-eight unique publications, assessing each technique for positive predictive value (PPV), false positive rates, and overall changes in practice patterns over time., Results: A total of 68 studies satisfied all criteria, with 3685 (3471, 94.2% confirmed) and 332 (285, 85.8% confirmed) patients tested for Cushing's disease and syndrome, respectively. Pooled analyses demonstrated an overall PPV of 89.3% (95%CI[83.6%, 94.0%]) in CRH stimulation diagnosis of Cushing disease. In desmopressin stimulation, our analyses demonstrated an overall PPV of 96.5% (95%CI[94.5%, 98.1%]) in diagnosis of Cushing disease. There was a significant decline in the use of CRH-stimulation IPSS in diagnosis of both Cushing disease (p = 0.0055) and Cushing syndrome (p = 0.013). Concurrently, there was a significant increase in the use of desmopressin-stimulation IPSS in diagnosis of both pathologies (p < 0.0001)., Conclusion: Our findings demonstrate significant changes in practice patterns with respect to IPSS stimulation technique. Our pooled analyses demonstrate improved diagnostic performance in desmopressin stimulation procedures relative to CRH stimulation procedures. Further multi-institutional studies with special attention to acquiring quality data for sensitivity, specificity, and other critical analyses are necessary to truly evaluate this promising technique., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
- Full Text
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28. Retinal ganglion cell-specific genetic regulation in primary open-angle glaucoma.
- Author
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Daniszewski M, Senabouth A, Liang HH, Han X, Lidgerwood GE, Hernández D, Sivakumaran P, Clarke JE, Lim SY, Lees JG, Rooney L, Gulluyan L, Souzeau E, Graham SL, Chan CL, Nguyen U, Farbehi N, Gnanasambandapillai V, McCloy RA, Clarke L, Kearns LS, Mackey DA, Craig JE, MacGregor S, Powell JE, Pébay A, and Hewitt AW
- Abstract
To assess the transcriptomic profile of disease-specific cell populations, fibroblasts from patients with primary open-angle glaucoma (POAG) were reprogrammed into induced pluripotent stem cells (iPSCs) before being differentiated into retinal organoids and compared with those from healthy individuals. We performed single-cell RNA sequencing of a total of 247,520 cells and identified cluster-specific molecular signatures. Comparing the gene expression profile between cases and controls, we identified novel genetic associations for this blinding disease. Expression quantitative trait mapping identified a total of 4,443 significant loci across all cell types, 312 of which are specific to the retinal ganglion cell subpopulations, which ultimately degenerate in POAG. Transcriptome-wide association analysis identified genes at loci previously associated with POAG, and analysis, conditional on disease status, implicated 97 statistically significant retinal ganglion cell-specific expression quantitative trait loci. This work highlights the power of large-scale iPSC studies to uncover context-specific profiles for a genetically complex disease., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)
- Published
- 2022
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29. Radiologic screening and surveillance in hereditary cancers.
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Clarke JE, Magoon S, Forghani I, Alessandrino F, D'Amato G, Jonczak E, and Subhawong TK
- Abstract
Hereditary cancer syndromes comprise an important subset of cancers caused by pathogenic germline mutations that can affect various organ systems. Radiologic screening and surveillance for solid tumors has emerged as a critical component of patient management in permitting early cancer detection. Although imaging surveillance may be tailored for organ-specific cancer risks, surveillance protocols frequently utilize whole-body MRI or PET/CT because of their ability to identify neoplasms in different anatomic regions in a single exam. In this review, we discuss the basic tenets of imaging screening and surveillance strategies in these syndromes, highlighting the more common neoplasms and their associated multimodality imaging findings., (© 2022 The Authors.)
- Published
- 2022
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30. Intracranial aneurysms in the infant population: an institutional case series and individual participant data meta-analysis.
- Author
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Clarke JE, Luther E, Oppenhuizen B, Leuchter JD, Ragheb J, Niazi TN, and Wang S
- Abstract
Objective: Infantile intracranial aneurysms are exceedingly rare. The goal of this study was to evaluate an institutional case series of infantile intracranial aneurysms, as well as those reported in the contemporary literature, to determine their demographics, presentation, management, and long-term outcome., Methods: A comprehensive literature review from 1980 to 2020 was performed to identify individual cases of intracranial aneurysms in the infantile population ≤ 2 years of age. Additional cases from the authors' institution were identified during the same time period. An individual participant data meta-analysis (IPDMA) was performed, abiding by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Patient demographic, radiographic, and clinical information was obtained. Descriptive statistical data were recorded, and multivariate logistic regression analyses were performed., Results: Patient data were obtained for 133 patients from 87 articles in the literature. Ten additional patients at the authors' institution were also identified, for a total of 143 patients included in the IPDMA. The majority (72.7%) of this cohort consisted of idiopathic aneurysms, while 13.3% were posttraumatic pseudoaneurysms, 9.8% were infectious mycotic aneurysms, and 4.2% were aneurysms associated with a systemic connective tissue disorder or vasculitis. The mean age at presentation was 6.6 months. The majority of infants (97.9%) harbored only 1 aneurysm, and hemorrhage was the most common presenting feature (78.3%). The mean aneurysm size was 14.4 mm, and giant aneurysms ≥ 25 mm comprised 12.9% of the cohort. Most aneurysms occurred in the anterior circulation (80.9%), with the middle cerebral artery (MCA) being the most commonly affected vessel (51.8%). Management strategies included open surgical aneurysm ligation (54.0%), endovascular treatment (35.0%), surgical decompression without aneurysm treatment (4.4%), and medical supportive management only (13.9%). Surgical aneurysm ligation was more commonly performed for MCA and anterior cerebral artery aneurysms (p = 0.004 and p = 0.015, respectively), while endovascular techniques were favored for basilar artery aneurysms (p = 0.042). The mean follow-up period was 29.9 months; 12.4% of the cohort died, and 67.0% had a favorable outcome (Glasgow Outcome Scale score of 5)., Conclusions: This study is, to the authors' knowledge, the largest analysis of infantile intracranial aneurysms to date. The majority were idiopathic aneurysms involving the anterior circulation. Surgical and endovascular techniques yielded equally favorable outcomes in this cohort. Long-term outcomes in the infantile population compared favorably to outcomes in adults.
- Published
- 2022
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31. The utility of congenital cardiac status to predict endoscopic third ventriculostomy and ventriculoperitoneal shunt failure in hydrocephalic infants.
- Author
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Lu VM, Leuchter JD, Clarke JE, Luther EM, Wang S, and Niazi TN
- Subjects
- Humans, Infant, Ventriculostomy methods, Treatment Outcome, Ventriculoperitoneal Shunt adverse effects, Retrospective Studies, Hypertension, Pulmonary complications, Hypertension, Pulmonary surgery, Hydrocephalus surgery, Hydrocephalus etiology, Heart Defects, Congenital surgery, Heart Defects, Congenital complications, Third Ventricle surgery, Neuroendoscopy methods
- Abstract
Objective: The effect of congenital cardiac status on endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) failure in hydrocephalic infants is unknown. Because cardiac status in infants can impact central venous pressure (CVP), it is possible that congenital heart disease (CHD) and congenital cardiac anomalies may render these cerebrospinal fluid diversion interventions more susceptible to failure. Correspondingly, the aim of this study was to determine how CHD and congenital cardiac anomalies may impact the failure of these initial interventions., Methods: A retrospective review of the Nationwide Inpatient Sample (NIS) database was conducted. Infants (aged < 1 year) with known congenital cardiac status managed with either ETV or VPS were included. Quantitative data were compared using either parametric or nonparametric methods, and failure rates were modeled using univariable and multivariable regression analyses., Results: A total of 18,763 infants treated with ETV or VPS for hydrocephalus were identified in our search, with ETV used to treat 7657 (41%) patients and VPS used to treat 11,106 (59%). There were 6722 (36%) patients who presented with CHD at admission, and a total of 25 unique congenital cardiac anomalies were detected across the cohort. Overall, the most common anomaly was patent ductus arteriosus (PDA) in 4990 (27%) patients, followed by atrial septal defect (ASD) in 2437 (13%) patients and pulmonary hypertension in 810 (4%) patients. With respect to initial intervention failure, 3869 (21%) patients required repeat surgical intervention during admission. This was significantly more common in the ETV group than the VPS group (36% vs 10%, p < 0.01). In both the ETV and VPS groups, CHD (p < 0.01), including all congenital cardiac anomalies, was an independent and significant predictor of failure. ASD (p < 0.01) and PDA (p < 0.01) both significantly predicted ETV failure, and PDA (p < 0.01) and pulmonary hypertension (p = 0.02) both significantly predicted VPS failure., Conclusions: These results indicate that congenital cardiac status predicts ETV and VPS failure in patients with infantile hydrocephalus. The authors hypothesized that this finding was primarily due to changes in CVP; however, this may not be completely universal across both interventions and all congenital cardiac anomalies. Future studies about optimization of congenital cardiac status with ETV and VPS are required to understand the practical significance of these findings.
- Published
- 2022
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32. Pediatric intracranial neurenteric cyst of the oculomotor nerve: a case-based review.
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Oppenhuizen B, Ragheb J, Leuchter JD, Clarke JE, Pelaez L, and Wang S
- Subjects
- Brain, Child, Humans, Magnetic Resonance Imaging, Male, Oculomotor Nerve, Central Nervous System Cysts, Neural Tube Defects
- Abstract
Background: Neurenteric cysts (NECs) of the central nervous system (CNS) are uncommon congenital entities arising from embryonal elements. Intracranial NECs in the pediatric population are rare., Methods: The authors describe the presentation, radiographic imaging, and pathologic findings of an 11-year-old boy with a right oculomotor nerve NEC. A literature review was performed to identify additional cases of pediatric intracranial NECs published in the English language, over the past 30 years (1990-2020). The authors discuss the presentation, investigations, management, and prognosis of this interesting entity., Results: We describe an 11-year-old boy who presented to neurosurgical attention with disconjugate gaze, anisocoria, and ptosis. Magnetic resonance imaging (MRI) demonstrated a lobulated, cystic, and peripherally enhancing mass involving the right oculomotor nerve. The patient underwent pterional craniotomy for drainage of the cyst and subtotal resection of the cyst wall. The tan-colored mass was displacing the basilar artery, compressing the cerebral peduncle, and adherent to the inferior surface of the tentorium. The lesion was within the oculomotor nerve and splitting the fibers, and the cystic contents were thick and mucinous. Histopathological examination of the specimen demonstrated a thin fibrous cyst wall with scattered inflammatory cells and lined by simple columnar epithelium containing mucin. The lining cells were immunoreactive with epithelial membrane antigen (EMA) and pan-keratin AE1/AE3. The diagnosis of a NEC was rendered. A comprehensive literature review of pediatric intracranial NECs yielded 46 additional lesions published in the literature, involving the skull base, posterior fossa, cerebral convexity, and cranial nerves. NECs present with local mass effect and less commonly, with aseptic meningitis or intracystic hemorrhage. Maximal safe GTR remains the mainstay management, although cyst drainage and marsupialization, cyst shunting, and fenestration of cystic contents into the ventricle or basal cisterns have been reported with variable success., Conclusion: CNS NECs are rare congenital entities; although they occur less frequently in the intracranial components compared to the spine, their diagnosis and management should be considered for intracranial cystic lesions. Maximal safe GTR is the mainstay treatment and frequently yields favorable outcomes., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)
- Published
- 2021
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33. Underwater noise from submarine turbidity currents.
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Hay AE, Hatcher MG, and Hughes Clarke JE
- Subjects
- Sound, Noise, Sand
- Abstract
Noise from turbidity currents flowing down the face of a fjord delta was measured underwater at frequencies from 1 to 1200 kHz. The noise spectra are consistent with sound generation by collisions among sand-sized particles. The spectra from the leading head extend to higher frequencies than those from the trailing body, indicating that collisions were between finer-grained particles in the head and coarser-grained particles in the body. Noise intensity increased 100-fold for a two-fold increase in head speed, consistent with the expected collision rate for granular materials in the high-flow gas-like phase and highly turbulent particle-laden flows.
- Published
- 2021
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34. Activity-directed expansion of a series of antibacterial agents.
- Author
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Leggott A, Clarke JE, Chow S, Warriner SL, O'Neill AJ, and Nelson A
- Subjects
- Anilides chemical synthesis, Anilides chemistry, Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents chemistry, Dose-Response Relationship, Drug, Microbial Sensitivity Tests, Molecular Structure, Structure-Activity Relationship, Anilides pharmacology, Anti-Bacterial Agents pharmacology, Staphylococcus aureus drug effects
- Abstract
The feasibility of using activity-directed synthesis to drive antibacterial discovery was investigated. An array of 220 Pd-catalysed microscale reactions was executed, and the crude product mixtures were evaluated for activity against Staphylococcus aureus. Scale-up of the hit reactions, purification and evaluation, enabled expansion of a class of antibacterial quinazolinones. The novel antibacterials had MICs from 0.016 μg mL-1 (i.e. 38 nM) to 2-4 μg mL-1 against S. aureus ATCC29213.
- Published
- 2020
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35. Rapidly-migrating and internally-generated knickpoints can control submarine channel evolution.
- Author
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Heijnen MS, Clare MA, Cartigny MJB, Talling PJ, Hage S, Lintern DG, Stacey C, Parsons DR, Simmons SM, Chen Y, Sumner EJ, Dix JK, and Hughes Clarke JE
- Abstract
Submarine channels are the primary conduits for terrestrial sediment, organic carbon, and pollutant transport to the deep sea. Submarine channels are far more difficult to monitor than rivers, and thus less well understood. Here we present 9 years of time-lapse mapping of an active submarine channel along its full length in Bute Inlet, Canada. Past studies suggested that meander-bend migration, levee-deposition, or migration of (supercritical-flow) bedforms controls the evolution of submarine channels. We show for the first time how rapid (100-450 m/year) upstream migration of 5-to-30 m high knickpoints can control submarine channel evolution. Knickpoint migration-related changes include deep (>25 m) erosion, and lateral migration of the channel. Knickpoints in rivers are created by external factors, such as tectonics, or base-level change. However, the knickpoints in Bute Inlet appear internally generated. Similar knickpoints are found in several submarine channels worldwide, and are thus globally important for how channels operate.
- Published
- 2020
- Full Text
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36. Direct Monitoring Reveals Initiation of Turbidity Currents From Extremely Dilute River Plumes.
- Author
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Hage S, Cartigny MJB, Sumner EJ, Clare MA, Hughes Clarke JE, Talling PJ, Lintern DG, Simmons SM, Silva Jacinto R, Vellinga AJ, Allin JR, Azpiroz-Zabala M, Gales JA, Hizzett JL, Hunt JE, Mozzato A, Parsons DR, Pope EL, Stacey CD, Symons WO, Vardy ME, and Watts C
- Abstract
Rivers (on land) and turbidity currents (in the ocean) are the most important sediment transport processes on Earth. Yet how rivers generate turbidity currents as they enter the coastal ocean remains poorly understood. The current paradigm, based on laboratory experiments, is that turbidity currents are triggered when river plumes exceed a threshold sediment concentration of ~1 kg/m
3 . Here we present direct observations of an exceptionally dilute river plume, with sediment concentrations 1 order of magnitude below this threshold (0.07 kg/m3 ), which generated a fast (1.5 m/s), erosive, short-lived (6 min) turbidity current. However, no turbidity current occurred during subsequent river plumes. We infer that turbidity currents are generated when fine sediment, accumulating in a tidal turbidity maximum, is released during spring tide. This means that very dilute river plumes can generate turbidity currents more frequently and in a wider range of locations than previously thought., (©2019. The Authors.)- Published
- 2019
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37. Control of Feeding Behavior by Cerebral Ventricular Volume Transmission of Melanin-Concentrating Hormone.
- Author
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Noble EE, Hahn JD, Konanur VR, Hsu TM, Page SJ, Cortella AM, Liu CM, Song MY, Suarez AN, Szujewski CC, Rider D, Clarke JE, Darvas M, Appleyard SM, and Kanoski SE
- Subjects
- Animals, Male, Neuropeptides metabolism, Rats, Rats, Sprague-Dawley, Synaptic Transmission, Cerebral Ventricles metabolism, Eating psychology, Feeding Behavior physiology, Hypothalamic Hormones cerebrospinal fluid, Melanins cerebrospinal fluid, Neurons metabolism, Pituitary Hormones cerebrospinal fluid
- Abstract
Classical mechanisms through which brain-derived molecules influence behavior include neuronal synaptic communication and neuroendocrine signaling. Here we provide evidence for an alternative neural communication mechanism that is relevant for food intake control involving cerebroventricular volume transmission of the neuropeptide melanin-concentrating hormone (MCH). Results reveal that the cerebral ventricles receive input from approximately one-third of MCH-producing neurons. Moreover, MCH cerebrospinal fluid (CSF) levels increase prior to nocturnal feeding and following chemogenetic activation of MCH-producing neurons. Utilizing a dual viral vector approach, additional results reveal that selective activation of putative CSF-projecting MCH neurons increases food intake. In contrast, food intake was reduced following immunosequestration of MCH endogenously present in CSF, indicating that neuropeptide transmission through the cerebral ventricles is a physiologically relevant signaling pathway for energy balance control. Collectively these results suggest that neural-CSF volume transmission signaling may be a common neurobiological mechanism for the control of fundamental behaviors., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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38. First wide-angle view of channelized turbidity currents links migrating cyclic steps to flow characteristics.
- Author
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Hughes Clarke JE
- Abstract
Field observations of turbidity currents remain scarce, and thus there is continued debate about their internal structure and how they modify underlying bedforms. Here, I present the results of a new imaging method that examines multiple surge-like turbidity currents within a delta front channel, as they pass over crescent-shaped bedforms. Seven discrete flows over a 2-h period vary in speed from 0.5 to 3.0 ms(-1). Only flows that exhibit a distinct acoustically attenuating layer at the base, appear to cause bedform migration. That layer thickens abruptly downstream of the bottom of the lee slope of the bedform, and the upper surface of the layer fluctuates rapidly at that point. The basal layer is inferred to reflect a strong near-bed gradient in density and the thickening is interpreted as a hydraulic jump. These results represent field-scale flow observations in support of a cyclic step origin of crescent-shaped bedforms.
- Published
- 2016
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39. Direct entry by RNase E is a major pathway for the degradation and processing of RNA in Escherichia coli.
- Author
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Clarke JE, Kime L, Romero A D, and McDowall KJ
- Subjects
- Escherichia coli Proteins metabolism, Molecular Sequence Data, RNA Cleavage, RNA Processing, Post-Transcriptional, Endoribonucleases metabolism, Escherichia coli enzymology, RNA, Messenger metabolism
- Abstract
Escherichia coli endoribonuclease E has a major influence on gene expression. It is essential for the maturation of ribosomal and transfer RNA as well as the rapid degradation of messenger RNA. The latter ensures that translation closely follows programming at the level of transcription. Recently, one of the hallmarks of RNase E, i.e. its ability to bind via a 5'-monophosphorylated end, was shown to be unnecessary for the initial cleavage of some polycistronic tRNA precursors. Here we show using RNA-seq analyses of ribonuclease-deficient strains in vivo and a 5'-sensor mutant of RNase E in vitro that, contrary to current models, 5'-monophosphate-independent, 'direct entry' cleavage is a major pathway for degrading and processing RNA. Moreover, we present further evidence that direct entry is facilitated by RNase E binding simultaneously to multiple unpaired regions. These simple requirements may maximize the rate of degradation and processing by permitting multiple sites to be surveyed directly without being constrained by 5'-end tethering. Cleavage was detected at a multitude of sites previously undescribed for RNase E, including ones that regulate the activity and specificity of ribosomes. A potentially broad role for RNase G, an RNase E paralogue, in the trimming of 5'-monophosphorylated ends was also revealed., (© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2014
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40. Adjacent single-stranded regions mediate processing of tRNA precursors by RNase E direct entry.
- Author
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Kime L, Clarke JE, Romero A D, Grasby JA, and McDowall KJ
- Subjects
- Escherichia coli enzymology, Escherichia coli genetics, RNA Cleavage, RNA Precursors chemistry, RNA, Transfer chemistry, Endoribonucleases metabolism, RNA Precursors metabolism, RNA Processing, Post-Transcriptional, RNA, Bacterial metabolism, RNA, Transfer metabolism
- Abstract
The RNase E family is renowned for being central to the processing and decay of all types of RNA in many species of bacteria, as well as providing the first examples of endonucleases that can recognize 5'-monophosphorylated ends thereby increasing the efficiency of cleavage. However, there is increasing evidence that some transcripts can be cleaved efficiently by Escherichia coli RNase E via direct entry, i.e. in the absence of the recognition of a 5'-monophosphorylated end. Here, we provide biochemical evidence that direct entry is central to the processing of transfer RNA (tRNA) in E. coli, one of the core functions of RNase E, and show that it is mediated by specific unpaired regions that are adjacent, but not contiguous to segments cleaved by RNase E. In addition, we find that direct entry at a site on the 5' side of a tRNA precursor triggers a series of 5'-monophosphate-dependent cleavages. Consistent with a major role for direct entry in tRNA processing, we provide additional evidence that a 5'-monophosphate is not required to activate the catalysis step in cleavage. Other examples of tRNA precursors processed via direct entry are also provided. Thus, it appears increasingly that direct entry by RNase E has a major role in bacterial RNA metabolism.
- Published
- 2014
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41. Assessing the quality of walking in adults with chronic pain: the development and preliminary psychometric evaluation of the Bath Assessment of Walking Inventory.
- Author
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Clarke JE and Eccleston C
- Subjects
- Adult, Aged, Biomechanical Phenomena, Chronic Disease psychology, Female, Gait Disorders, Neurologic etiology, Humans, Male, Middle Aged, Neuropsychological Tests, Pain Measurement methods, Pain, Intractable complications, Predictive Value of Tests, Psychology, Reproducibility of Results, Surveys and Questionnaires, Activities of Daily Living psychology, Exercise Tolerance, Gait Disorders, Neurologic psychology, Pain, Intractable psychology, Psychometrics methods, Walking psychology
- Abstract
Walking is fundamental to many activities that are detrimentally affected by chronic pain. When in pain, people adapt how they walk. This article reports the development of an observational rating scale for the assessment of the quality of walking in adults with chronic pain called the Bath Assessment of Walking Inventory. The BAWI was designed explicitly for clinical and research use. A review of the literature on movement assessment, and a professional focus group, yielded 36 items capturing specific characteristics of walking that were organised into 11 domains. Investigation into the psychometric properties reduced the final measure to 23 items in 8 domains that demonstrated good internal consistency (Cronbach 0.71) and adequate intra (Kappa 0.61-0.98) and inter-rater reliability (Kappa 0.61-0.98). Validity was established in comparison with well-used measures of functioning. Further independent study is required to develop this instrument. A robust measure of walking will enable accurate clinical assessment, and the investigation of psychosocial and biomechanical influences on walking quality, and of the communicative function of pain related movement.
- Published
- 2009
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42. A case of prolonged type 1 hypersensitivity reaction to pegfilgrastim.
- Author
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Hanna GG, Edgar D, and Clarke JE
- Subjects
- Adult, Anaphylaxis therapy, Colony-Stimulating Factors adverse effects, Female, Filgrastim, Humans, Neutropenia prevention & control, Polyethylene Glycols, Recombinant Proteins, Anaphylaxis etiology, Granulocyte Colony-Stimulating Factor adverse effects
- Published
- 2008
- Full Text
- View/download PDF
43. Psoriatic arthritis in a military aviator.
- Author
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Sulit DJ and Clarke JE
- Subjects
- Adult, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Arthritis, Psoriatic complications, Chronic Disease, Etanercept, Humans, Immunoglobulin G therapeutic use, Male, Receptors, Tumor Necrosis Factor therapeutic use, United States, Aerospace Medicine, Arthritis, Psoriatic drug therapy, Aviation, Military Medicine, Military Personnel
- Abstract
Psoriatic arthritis is a chronic spondyloarthropathy whose pathogenesis is unknown. We present a case of a naval flight officer who presented with chronic psoriatic arthritis, which ultimately became well controlled with etanercept treatment. The naval flight officer was granted military aeromedical waivers for psoriatic arthritis, cutaneous psoriasis, and chronic medication use. We also review the medical literature on psoriatic arthritis disease and etanercept and discuss their aeromedical implications in military aviation.
- Published
- 2005
44. Geomorphology, acoustic backscatter, and processes in Santa Monica Bay from multibeam mapping.
- Author
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Gardner JV, Dartnell P, Mayer LA, and Hughes Clarke JE
- Subjects
- Acoustics, California, Geological Phenomena, Water Supply, Environmental Monitoring, Geology
- Abstract
Santa Monica Bay was mapped in 1996 using a high-resolution multibeam system, providing the first substantial update of the submarine geomorphology since the initial compilation by Shepard and Emery [(1941) Geol. Soc. Amer. Spec. Paper 31]. The multibeam mapping generated not only high-resolution bathymetry, but also coregistered, calibrated acoustic backscatter at 95 kHz. The geomorphology has been subdivided into six provinces; shelf, marginal plateau, submarine canyon, basin slope, apron, and basin. The dimensions, gradients, and backscatter characteristics of each province is described and related to a combination of tectonics, climate, sea level, and sediment supply. Fluctuations of eustatic sea level have had a profound effect on the area; by periodically eroding the surface of Santa Monica plateau, extending the mouth of the Los Angeles River to various locations along the shelf break, and by connecting submarine canyons to rivers. A wetter glacial climate undoubtedly generated more sediment to the rivers that then transported the increased sediment load to the low-stand coastline and canyon heads. The trends of Santa Monica Canyon and several bathymetric highs suggest a complex tectonic stress field that has controlled the various segments. There is no geomorphic evidence to suggest Redondo Canyon is fault controlled. The San Pedro fault can be extended more than 30 km to the northwest by the alignment of a series of bathymetric highs and abrupt changes in direction of channel thalwegs.
- Published
- 2003
- Full Text
- View/download PDF
45. In vivo temperature dependence of cyclic and pseudocyclic electron transport in barley.
- Author
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Clarke JE and Johnson GN
- Subjects
- Biological Transport, Active, Chlorophyll metabolism, Electron Transport physiology, Fluorescence, Hydrogen-Ion Concentration, Light, Light-Harvesting Protein Complexes, Oxidation-Reduction, Photosynthetic Reaction Center Complex Proteins radiation effects, Plant Leaves physiology, Plant Leaves radiation effects, Thylakoids radiation effects, Hordeum physiology, Oxygen metabolism, Photosynthetic Reaction Center Complex Proteins metabolism, Temperature, Thylakoids physiology
- Abstract
The effect of temperature on the rate of electron transfer through photosystems I and II (PSI and PSII) was investigated in leaves of barley (Hordeum vulgare L.). Measurements of PSI and PSII photochemistry were made in 21% O2 and in 2% O2, to limit electron transport to O2 in the Mehler reaction. Measurements were made in the presence of saturating CO2 concentrations to suppress photorespiration. It was observed that the O2 dependency of PSII electron transport is highly temperature dependent. At 10 degrees C, the quantum yield of PSII (phi PSII) was insensitive to O2 concentration, indicating that there was no Mehler reaction operating. At high temperatures (> 25 degrees C) a substantial reduction in phi PSII was observed when the O2 concentration was reduced. However, under the same conditions, there was no effect of O2 concentration on the delta pH-dependent process of non-photochemical quenching. The rate of electron transport through PSI was also found to be independent of O2 concentration across the temperature range. We conclude that the Mehler reaction is not important in maintaining a thylakoid proton gradient that is capable of controlling PSII activity, and present evidence that cyclic electron transport around PSI acts to maintain membrane energisation at low temperature.
- Published
- 2001
- Full Text
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46. A large-animal model to evaluate the clinical potential of fetal pig pancreas fragment transplantation.
- Author
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Hawthorne WJ, Cachia AR, Walters SN, Patel AT, Clarke JE, O'Connell PJ, Chapman JR, and Allen RD
- Subjects
- Animals, Biopsy, Chromogranins analysis, Diabetes Mellitus, Type 1 surgery, Fetal Tissue Transplantation immunology, Fibrosis, Graft Rejection immunology, Graft Rejection pathology, Graft Survival, Immunosuppression Therapy, Insulin analysis, Models, Animal, Necrosis, Pancreas Transplantation immunology, Swine, T-Lymphocytes immunology, Transplantation, Homologous, Fetal Tissue Transplantation methods, Pancreas Transplantation methods
- Abstract
The long-term goal of this study is to assess the feasibility of using fetal pig pancreas fragment (FPPF) transplantation to treat patients with type I diabetes. Using the highly inbred Westran Pigs, our initial aim was to establish a rejection-free transplant model of FPPF grafted into sibling recipient pigs without immunosuppression. FPPFs were isolated from 80-100-day-old fetuses of either Westran Pigs or outbred pigs and transplanted into the thymus, spleen, liver, or kidney of the recipient Westran pig. Biopsies were taken from each transplant site at set time points and assessed histologically for islet viability, rejection, and endocrine function. Fifty-eight fetal donors were used to transplant 16 recipient pigs. A nonspecific inflammation was seen for both outbred and inbred FPPF donor tissue at day 3 and was considered a response to ischemic necrosis. However, all the transplanted outbred FPPF donor tissue was acutely rejected and lost by day 10-14. In contrast, inbred FPPF tissue showed little evidence of graft necrosis after 3 days, and growth and formation of epithelial islet cell nest-like structures were seen to 28 days after transplantation. With time after transplantation, increasing amounts of insulin immunoperoxidase staining was seen together with chromogranin and somatostatin staining. In summary, this study confirms the potential of the Westran pig to answer the unproven ability of fetal pancreatic tissue to reverse type I diabetes in a large animal model.
- Published
- 2000
- Full Text
- View/download PDF
47. Courting disaster? A survey of the autopsy service provided by district surgeons in Kwazulu-Natal.
- Author
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Dada MA and Clarke JE
- Subjects
- Adult, Clinical Competence, Documentation, Expert Testimony, Forensic Medicine education, Forensic Medicine organization & administration, Humans, Middle Aged, South Africa, Autopsy standards, Quality of Health Care
- Abstract
Aim: To provide information on the overall quality of the autopsy service provided by district surgeons in KwaZulu-Natal (KZN) and in particular to identify factors which may have a negative impact on the judicial process., Method: Confidential questionnaires were sent to 73 district surgeons and 216 legal practitioners including prosecution advocates, regional court prosecutors, defence advocates and attorneys. One hundred and twenty (43%) replies (47 doctors and 73 lawyers) were suitable for analysis., Results: District surgeons have no shortage of experience or maturity but their performance is hampered by the following: lack of appropriate training in forensic pathology; high case load; inadequate facilities and support staff; and lack of access to ancillary services., Conclusion: This study has shown that the standard of autopsy services by district surgeons varies considerably. Overall, there is evidence that inadequacies on the part of district surgeons have negative repercussions for the criminal justice system. Urgent attention should be given to implement training programmes for the district surgeons and to improve service conditions.
- Published
- 2000
48. Rural home care of a technology-dependent infant.
- Author
-
Clarke JE
- Subjects
- Family Practice, Home Care Services economics, Humans, Infant, Newborn, Male, Parents education, Parents psychology, Patient Care Team organization & administration, Goldenhar Syndrome therapy, Home Care Services organization & administration, Medical Laboratory Science, Rural Health
- Abstract
A multidisciplinary approach is necessary to prepare for home care of technology-dependent infants. The environment must protect, support, and promote the physical, cognitive, and social growth and development of these infants. Parents and caregivers of technology-dependent infants should be taught cardiopulmonary resuscitation and should be helped to develop a plan for obtaining emergency medical assistance.
- Published
- 1995
49. Do workup before sedating an unruly patient.
- Author
-
Ellinoy BR and Clarke JE
- Subjects
- Humans, Ethics, Pharmacy, Hypnotics and Sedatives administration & dosage, Mental Disorders diagnosis
- Published
- 1994
50. A modified Kloehn bow for cranio-maxillary fixation.
- Author
-
Chate RA and Clarke JE
- Subjects
- Equipment Design, Humans, Malocclusion surgery, Maxilla surgery, Orthodontic Appliances, Osteotomy instrumentation
- Published
- 1992
- Full Text
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