575 results on '"M. Lockwood"'
Search Results
2. The Impact of Perioperative and Operative Variables on Early Postoperative Complications Following Primary Hypospadias Repair
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Douglas W. Storm, Gina M. Lockwood, Megan A. Bonnett, Benjamin J. Cooper, Logan M. Harris, and Christopher S. Cooper
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Male ,Hypospadias ,Urologic Surgical Procedures, Male ,Postoperative Complications ,Treatment Outcome ,Urethra ,Urology ,Humans ,Infant ,Retrospective Studies - Abstract
To evaluate possible risk factors for complications following primary hypospadias repair relative to factors associated with timing of hypospadias repair in terms of case order, morning or afternoon scheduling, perioperative delays, and surgeon's daily work schedule as well as individual operative techniques.We retrospectively reviewed charts of 422 boys undergoing primary hypospadias repair with a sutured urethroplasty by 1 of 3 surgeons over a 10-year period and the surgeon's daily schedule.The median age and IQR of the patients at time of operation was 0.79 (0.57) years, and median follow-up was 259 (664) days. A significant increase in the rate of any complication was noted with morning vs afternoon cases for the group overall with morning cases having a hazard 2.3 times higher than afternoon cases (P =.012). Additionally, there was a significant increase in hazard of complication with increasing difference in time between actual procedure duration vs scheduled duration, with hazard of complication increasing 5% for each increase of 15 minutes of surgical time (P =.043).A variety of previously identified potential risk factors for hypospadias complications were identified. Our analysis also demonstrated variability in level of risk of different factors between surgeons, reinforcing the utility of surgeons monitoring their own results in response to changes in technique. Novel potential risk factors for some surgeons identified in our study included an increased risk of complications when the hypospadias was done in the morning rather than the afternoon and when the procedure lasted longer than scheduled.
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- 2022
3. Does Antimicrobial Prophylaxis in Patients with Specific Comorbidities Reduce the Risk of Infection after Simple Cystourethroscopy?
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Brenton G. Sherwood, Elizabeth B. Takacs, Bradley A. Ford, Sarah L. Mott, Bradley T. Loeffler, and Gina M. Lockwood
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Urology - Published
- 2022
4. Evidence-based procedures to improve the reliability of circulating miRNA biomarker assays
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Sarah R. Greytak, Kelly B. Engel, Dave S. B. Hoon, Kevin M. Elias, Christina M. Lockwood, Ping Guan, and Helen M. Moore
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Biochemistry (medical) ,Clinical Biochemistry ,General Medicine - Abstract
Circulating cell-free microRNAs (cfmiRNA) are an emerging class of biomarkers that have shown great promise in the clinical diagnosis, treatment, and monitoring of several pathological conditions, including cancer. However, validation and clinical implementation of cfmiRNA biomarkers has been hindered by the variability introduced during different or suboptimal specimen collection and handling practices. To address the need for standardization and evidence-based guidance, the National Cancer Institute (NCI) developed a new Biospecimen Evidenced-Based Practices (BEBP) document, entitled “Cell-free miRNA (cfmiRNA): Blood Collection and Processing”. The BEBP, the fourth in the document series, contains step-by-step procedural guidelines on blood collection, processing, storage, extraction, and quality assessment that are tailored specifically for cfmiRNA analysis of plasma and serum. The workflow outlined in the BEBP is based on the available literature and recommendations of an expert panel. The BEBP contains the level of detail required for development of evidence-based standard operating procedures (SOPs) as well as the flexibility needed to accomodate (i) discovery- and inquiry-based studies and (ii) the different constraints faced by research labs, industry, clinical and academic institutions to foster widespread implementation. Guidance from the expert panel also included recommendations on study design, validating changes in workflow, and suggested quality thresholds to delineate meaningful changes in cfmiRNA levels. The NCI cfmiRNA: Blood Collection and Processing BEBP is available here as supplementary information as well as through the NCI Biorepositories and Biospecimen Research Branch (BBRB) (https://biospecimens.cancer.gov/resources/bebp.asp).
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- 2023
5. Diagnosis of Ovarian Carcinoma Homologous Recombination DNA Repair Deficiency From Targeted Gene Capture Oncology Assays
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Niklas Krumm, Nithisha S. Khasnavis, Marc Radke, Kalyan Banda, Helen R. Davies, Christopher Pennil, Kathryn McLean, Vera A. Paulson, Eric Q. Konnick, Winslow C. Johnson, Grogan Huff, Serena Nik-Zainal, Elizabeth M. Swisher, Christina M. Lockwood, and Stephen J. Salipante
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Cancer Research ,Oncology - Abstract
PURPOSE Homologous recombination DNA repair deficiency (HRD) is a therapeutic biomarker for sensitivity to platinum and poly(ADP-ribose) polymerase inhibitor therapies in breast and ovarian cancers. Several molecular phenotypes and diagnostic strategies have been developed to assess HRD; however, their clinical implementation remains both technically challenging and methodologically unstandardized. METHODS We developed and validated an efficient and cost-effective strategy for HRD determination on the basis of calculation of a genome-wide loss of heterozygosity (LOH) score through targeted, hybridization capture and next-generation DNA sequencing augmented with 3,000 common, polymorphic single-nucleotide polymorphism (SNP) sites distributed genome-wide. This approach requires minimal sequence reads and can be readily integrated into targeted gene capture workflows already in use for molecular oncology. We interrogated 99 ovarian neoplasm-normal pairs using this method and compared results with patient mutational genotypes and orthologous predictors of HRD derived from whole-genome mutational signatures. RESULTS LOH scores of ≥11% had >86% sensitivity for identifying tumors with HRD-causing mutations in an independent validation set (90.6% sensitivity for all specimens). We found strong agreement of our analytic approach with genome-wide mutational signature assays for determining HRD, yielding an estimated 96.7% sensitivity and 50% specificity. We observed poor concordance with mutational signatures inferred using only mutations detected by the targeted gene capture panel, suggesting inadequacy of the latter approach. LOH score did not significantly correlate with treatment outcomes. CONCLUSION Targeted sequencing of genome-wide polymorphic SNP sites can be used to infer LOH events and subsequently diagnose HRD in ovarian tumors. The methods presented here are readily generalizable to other targeted gene oncology assays and could be adapted for HRD diagnosis in other tumor types.
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- 2023
6. Clinical Testing for Tumor Cell-Free DNA: College of American Pathologists Proficiency Programs Reveal Practice Trends
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Kelly A. Devereaux, Rhona J. Souers, Jason D. Merker, Neal I. Lindeman, Rondell P. Graham, Meera R. Hameed, Patricia Vasalos, Joel T. Moncur, Christina M. Lockwood, and Rena R. Xian
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Medical Laboratory Technology ,General Medicine ,Pathology and Forensic Medicine - Abstract
Context.— Clinical testing for tumor cell-free DNA (cfDNA) has evolved rapidly, but no practice guidelines exist. Objective.— To summarize cfDNA laboratory practices based on self-reporting and assess preanalytical, analytical, and postanalytical trends that may influence the quality, accuracy, and consistency of cfDNA testing. Design.— Data were derived from the College of American Pathologists cfDNA proficiency testing program submitted by 101 participating laboratories from 2018 to 2019. Results.— Most laboratories performing clinical circulating tumor DNA testing are commercial/nonhospital (71.2%; 72 of 101) and international (77.2%; 78 of 101) laboratories. Commercial laboratories had higher monthly test volumes than hospital-based laboratories (median, 36 versus 7–8) and tended to have larger gene panels (median, 50 versus 11 genes) when panel-based testing was offered. The main clinical indications include therapy selection and treatment/disease monitoring. Plasma is the most commonly accepted specimen, which is predominantly collected in cell-stabilizing tubes. Equal proportions of laboratories use next-generation sequencing (NGS) and non-NGS methods to assess key genes, including EGFR, BRAF, KRAS, NRAS, and IDH1. Most laboratories reported a lower limit of detection (LLOD) of 0.5%, variant allele frequency or less, which did not differ by method, NGS or non-NGS, except for EGFR. Sixty-five percent (17 of 26) of laboratories using the US Food and Drug Administration (FDA)-approved non-NGS EGFR assay report analytical sensitivities higher than 0.5%, as compared to 15% (16 of 104) of laboratories using an alternative NGS or non-NGS method. There is also a wider range in LLODs obtained for the FDA-approved EGFR assay than nonapproved assays. Conclusions.— These results highlight emerging practice trends and serve as a foundation to initiate future practice recommendations.
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- 2022
7. Table S1 from Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIG/DIA) Are Distinct Entities with Frequent BRAFV600 Mutations
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Jeffrey G. Ojemann, Richard G. Ellenbogen, Amy Lee, Eric C. Holland, J. Russell Geyer, James M. Olson, Chibawanye Ene, Shelly Wang, Aria Fallah, Andrey Korshunov, David Capper, Lukas Chavez, Christina M. Lockwood, Sarah E.S. Leary, Bonnie L. Cole, Isaac Joshua Abecassis, David T.W. Jones, and Anthony C. Wang
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SCH Clinical and Sequencing Data
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- 2023
8. Infantile ZFTA Fusion–Positive Tumor of the Posterior Fossa: Molecular Tumor Board
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Vera A. Paulson, Yajuan J. Liu, He Fang, Sam R. Browd, Jason S. Hauptman, Jason Wright, Christina M. Lockwood, Sarah E. S. Leary, and Bonnie L. Cole
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Cancer Research ,Oncology - Published
- 2023
9. Response to letter to the editor re what is the angle of a banana? The difficulty in reliable assessment of hypospadias chordee
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Christopher S. Cooper, Gina M. Lockwood, Angelena B. Edwards, and Douglas W. Storm
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Urology ,Pediatrics, Perinatology and Child Health - Published
- 2023
10. Recalibration of the Sunspot-Number: Status Report
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F. Clette, L. Lefèvre, T. Chatzistergos, H. Hayakawa, V. M. S. Carrasco, R. Arlt, E. W. Cliver, T. Dudok de Wit, T. K. Friedli, N. Karachik, G. Kopp, M. Lockwood, S. Mathieu, A. Muñoz-Jaramillo, M. Owens, D. Pesnell, A. Pevtsov, L. Svalgaard, I. G. Usoskin, L. van Driel-Gesztelyi, and J. M. Vaquero
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Astrophysics - Solar and Stellar Astrophysics ,Physics - Space Physics ,Space and Planetary Science ,FOS: Physical sciences ,Astronomy and Astrophysics ,Solar and Stellar Astrophysics (astro-ph.SR) ,Space Physics (physics.space-ph) - Abstract
We report progress on the ongoing recalibration of the Wolf sunspot number (SN) and Group sunspot number (GN) following the release of version 2.0 of SN in 2015. This report constitutes both an update of the efforts reported in the 2016 Topical Issue of Solar Physics and a summary of work by the International Space Science Institute (ISSI) International Team formed in 2017 to develop optimal SN and GN re-construction methods while continuing to expand the historical sunspot number database. Significant progress has been made on the database side while more work is needed to bring the various proposed SN and (primarily) GN reconstruction methods closer to maturity, after which the new reconstructions (or combinations thereof) can be compared with (a) ``benchmark'' expectations for any normalization scheme (e.g., a general increase in observer normalization factors going back in time), and (b) independent proxy data series such as F10.7 and the daily range of variations of Earth's undisturbed magnetic field. New versions of the underlying databases for SN and GN will shortly become available for years through 2022 and we anticipate the release of next versions of these two time series in 2024., 21 figures, 4 tables. To be published in Solar Physics
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- 2023
11. Universal Time Variations in the Magnetosphere and the Effect of CME Arrival Time: Analysis of the February 2022 Event that Led to the Loss of Starlink Satellites
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M. Lockwood, M. J. Owens, and L. A. Barnard
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Geophysics ,Space and Planetary Science - Published
- 2023
12. What is the angle of a banana? The difficulty in reliable assessment of hypospadias chordee
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Christopher S. Cooper, Gina M. Lockwood, Angelena B. Edwards, Sarah S. Perry, and Douglas W. Storm
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Urology ,Pediatrics, Perinatology and Child Health - Published
- 2023
13. Pilot study of a home use cystomanometer in patients with a neurogenic bladder
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Christopher S. Cooper, Megan A. Bonnett, Christopher E. Ortman, Denise Juhr, Douglas W. Storm, and Gina M. Lockwood
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Urodynamics ,Urology ,Urinary Bladder ,Pediatrics, Perinatology and Child Health ,Humans ,Pilot Projects ,Urinary Bladder, Neurogenic - Abstract
A novel device, the cystomanometer, was developed for home bladder pressure monitoring in patients with neurogenic bladder.To report initial experience and proof of concept with home use of the cystomanometer.Patients were asked to use the device twice daily for two weeks.Fourteen patients with neurogenic bladder were enrolled.The cystomanometer initially functioned well and transmitted data to a smartphone and to the hospital server. However, over 50% of devices broke.We report the first home use of a handheld electronic cystomanometer with wireless data transmission to a smartphone and hospital database.
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- 2022
14. Diagnostic testing approaches for the identification of patients with TRK fusion cancer prior to enrollment in clinical trials investigating larotrectinib
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Erin R. Rudzinski, Jaclyn Hechtman, Sinchita Roy-Chowdhuri, Marion Rudolph, Christina M. Lockwood, Josh Silvertown, Justyna Wierzbinska, Kui Shen, Ricarda Norenberg, Hendrik Nogai, David S. Hong, Alexander Drilon, and Theodore W. Laetsch
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Adult ,Male ,Cancer Research ,Oncogene Proteins, Fusion ,Clinical Trials, Phase II as Topic ,Neoplasms ,Genetics ,Humans ,Receptor, trkB ,Receptor, trkC ,Precision Medicine ,Receptor, trkA ,Child ,Molecular Biology ,Diagnostic Techniques and Procedures ,In Situ Hybridization, Fluorescence ,Membrane Glycoproteins ,Clinical Trials, Phase I as Topic ,Sequence Analysis, RNA ,Patient Selection ,High-Throughput Nucleotide Sequencing ,Sequence Analysis, DNA ,Microarray Analysis ,Pyrimidines ,Pyrazoles ,Female - Abstract
NTRK gene fusions are targetable oncogenic drivers independent of tumor type. Prevalence varies from highly recurrent in certain rare tumors to1% in common cancers. The selective TRK inhibitor larotrectinib was shown to be highly active in adult and pediatric patients with tumors harboring NTRK gene fusions.We examined the techniques used by local sites to detect tumor NTRK gene fusions in patients enrolled in clinical trials of larotrectinib. We also report the characteristics of the detected fusions in different tumor types.The analysis included 225 patients with 19 different tumor types. Testing methods used were next-generation sequencing (NGS) in 196 of 225 tumors (87%); this was RNA-based in 96 (43%); DNA-based in 53 (24%); DNA/RNA-based in 46 (20%) and unknown in 1 (1%); FISH in 14 (6%) and PCR-based in 12 (5%). NanoString, Sanger sequencing and chromosome microarray were each utilized once (1%). Fifty-four different fusion partners were identified, 39 (72%) of which were unique occurrences.The most common local testing approach was RNA-based NGS. Many different NTRK gene fusions were identified with most occurring at low frequency. This supports the need for validated and appropriate testing methodologies that work agnostic of fusion partners.
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- 2022
15. Beyond Health: Nonhealth Risk and the Value of Disability Insurance
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Manasi Deshpande and Lee M. Lockwood
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Economics and Econometrics - Abstract
The public debate over disability insurance has centered on concerns about individuals without severe health conditions receiving benefits. We go beyond health risk alone to quantify the overall insurance value of U.S. disability programs, including value from insuring nonhealth risk. We find that disability recipients, especially those with less‐severe health conditions, are much more likely to have experienced a wide variety of nonhealth shocks than nonrecipients. Selection into disability receipt on the basis of nonhealth shocks is so strong among individuals with less‐severe health conditions that by many measures less‐severe recipients are worse off than more‐severe recipients. As a result, under baseline assumptions, benefits to less‐severe recipients have an annual surplus value (insurance benefit less efficiency cost) over cost‐equivalent tax cuts of $7700 per recipient, about three‐fourths that of benefits to more‐severe recipients ($9900). Insurance against nonhealth risk accounts for about one‐half of the value of U.S. disability programs.
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- 2022
16. The utility of renal medullary pyramidal thickness measurements on the first and second postnatal ultrasound in infants with congenital hydronephrosis
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Kathleen Kwiatkowski, Tomas Lence, Angelena B. Edwards, Gina M. Lockwood, Douglas W. Storm, Hanh T.D. Pham, and Christopher S. Cooper
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Urology ,Pediatrics, Perinatology and Child Health - Published
- 2023
17. Opioids and pediatric urology: A prospective study evaluating prescribing habits and patient postoperative pain and narcotic utilization
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Tomas Lence, Robert Thinnes, Alexander J. Foster, Christopher S. Cooper, Gina M. Lockwood, Patrick Ten Eyck, Zachary Rye, Chaorong Wu, Denise Juhr, and Douglas W. Storm
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Urology ,Pediatrics, Perinatology and Child Health - Published
- 2023
18. BLM overexpression as a predictive biomarker for CHK1 inhibitor response in PARP inhibitor–resistant BRCA-mutant ovarian cancer
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Nitasha Gupta, Tzu-Ting Huang, Jayakumar R. Nair, Daniel An, Grant Zurcher, Erika J. Lampert, Ann McCoy, Ashley Cimino-Mathews, Elizabeth M. Swisher, Marc R. Radke, Christina M Lockwood, Jonathan B. Reichel, Chih-Yuan Chiang, Kelli M. Wilson, Ken Chih-Chien Cheng, Darryl Nousome, and Jung-Min Lee
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PARP inhibitors (PARPis) have changed the treatment paradigm inBRCA-mutant high-grade serous ovarian carcinoma (HGSC). However, most patients eventually develop resistance to PARPis, highlighting an unmet need for novel therapeutic strategies. Using high-throughput drug screens, we identified ATR/CHK1 pathway inhibitors as cytotoxic, and further validated monotherapy activity of the CHK1 inhibitor (CHK1i), prexasertib, in PARPi-resistantBRCA-mutant HGSC cells and animal models. As a proof-of-concept trial, we conducted a phase II study of prexasertib inBRCA-mutant HGSC patients. The treatment was well-tolerated but yielded an objective response rate of 6% (1/17; 1 PR) in patients with prior PARPi treatment. Exploratory biomarker analyses revealed that replication stress and fork stabilization were associated with clinical benefit to CHK1i. In particular, overexpression ofBLM, andCCNE1overexpression or copy number gain/amplification were seen in patients deriving durable benefit from CHK1i. Our findings suggest replication fork–related biomarkers should be further evaluated for CHK1i sensitivity in HGSC.One Sentence SummaryOverexpression of RecQ helicase BLM is a predictive biomarker for CHK1 inhibitor response in PARP inhibitor–resistantBRCA-mutant ovarian cancer.
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- 2022
19. SwabExpress: An End-to-End Protocol for Extraction-Free COVID-19 Testing
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Kaitlyn A Barrow, Sarah Heidl, Elisabeth Brandstetter, Deborah A. Nickerson, Rachel E. Geyer, Sanjay Srivatsan, Eric Q. Konnick, Nahum Smith, Mark J. Rieder, Sriram Kosuri, Helen Y. Chu, Lea M. Starita, Misja Ilcisin, Shari Cho, L.M. Rich, Luis Gamboa, Denise J. McCulloch, Jay Shendure, Jeremy Stone, Jordan Opsahl, Ashley E. Kim, Caitlin R Wolf, Christina M. Lockwood, Peter D Han, Melissa Truong, Trevor Bedford, Wei Chen, Evan McDermot, Beth Martin, Sarah L Sohlberg, Brian Pfau, Jase Gehring, Katrina van Raay, Jason S Debley, and Weizhi Zhong
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Coronavirus disease 2019 (COVID-19) ,Computer science ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Clinical Biochemistry ,Nucleic Acid Testing ,Real-Time Polymerase Chain Reaction ,Sensitivity and Specificity ,Specimen Handling ,Transport medium ,medicine ,Humans ,Protocol (science) ,Clinical Laboratory Techniques ,SARS-CoV-2 ,business.industry ,Biochemistry (medical) ,Extraction (chemistry) ,COVID-19 ,AcademicSubjects/SCI01290 ,Anterior nares ,Editorial ,medicine.anatomical_structure ,End to end protocol ,COVID-19 Nucleic Acid Testing ,Embedded system ,RNA, Viral ,AcademicSubjects/MED00530 ,AcademicSubjects/SCI00980 ,business ,AcademicSubjects/MED00690 - Abstract
Background The urgent need for massively scaled clinical testing for SARS-CoV-2, along with global shortages of critical reagents and supplies, has necessitated development of streamlined laboratory testing protocols. Conventional nucleic acid testing for SARS-CoV-2 involves collection of a clinical specimen with a nasopharyngeal swab in transport medium, nucleic acid extraction, and quantitative reverse-transcription PCR (RT–qPCR). As testing has scaled across the world, the global supply chain has buckled, rendering testing reagents and materials scarce. To address shortages, we developed SwabExpress, an end-to-end protocol developed to employ mass produced anterior nares swabs and bypass the requirement for transport media and nucleic acid extraction. Methods We evaluated anterior nares swabs, transported dry and eluted in low-TE buffer as a direct-to-RT–qPCR alternative to extraction-dependent viral transport media. We validated our protocol of using heat treatment for viral inactivation and added a proteinase K digestion step to reduce amplification interference. We tested this protocol across archived and prospectively collected swab specimens to fine-tune test performance. Results After optimization, SwabExpress has a low limit of detection at 2–4 molecules/µL, 100% sensitivity, and 99.4% specificity when compared side by side with a traditional RT–qPCR protocol employing extraction. On real-world specimens, SwabExpress outperforms an automated extraction system while simultaneously reducing cost and hands-on time. Conclusion SwabExpress is a simplified workflow that facilitates scaled testing for COVID-19 without sacrificing test performance. It may serve as a template for the simplification of PCR-based clinical laboratory tests, particularly in times of critical shortages during pandemics.
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- 2021
20. Predictors of mortality and tumor recurrence in desmoplastic infantile ganglioglioma and astrocytoma—and individual participant data meta-analysis (IPDMA)
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Anthony C. Wang, Alexander G. Weil, Jeffrey G. Ojemann, George M. Ibrahim, Chibawanye I. Ene, Sarah Leary, Richard G. Ellenbogen, James Olson, I Joshua Abecassis, Shelly Wang, Bonnie Cole, Aria Fallah, Matthew Z. Sun, J. Russell Geyer, and Christina M. Lockwood
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Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Neurology ,medicine.medical_treatment ,Oncology and Carcinogenesis ,Desmoplastic ,Astrocytoma ,Infantile ,Article ,BRAF ,Ganglioglioma ,Internal medicine ,medicine ,Humans ,Oncology & Carcinogenesis ,Cancer ,Chemotherapy ,Brain Neoplasms ,business.industry ,Proportional hazards model ,Neurosciences ,Infant ,medicine.disease ,Tumor Pathology ,Neoplasm Recurrence ,Good Health and Well Being ,Local ,Meta-analysis ,Cohort ,Female ,Neurology (clinical) ,Neoplasm Recurrence, Local ,business ,Meningeal Carcinomatosis - Abstract
PURPOSE: Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are classified together as grade I neuronal and mixed neuronal-glial tumor of the central nervous system by the World Health Organization (WHO). These tumors are rare and have not been well characterized in terms of clinical outcomes. We aimed to identify clinical predictors of mortality and tumor recurrence/progression by performing an individual patient data meta-analysis (IPDMA) of the literature. METHODS: A systematic literature review from 1970 to 2020 was performed, and individualized clinical data for patients diagnosed with DIA/DIG were extracted. Aggregated data were excluded from collection. Outcome measures of interest were mortality and tumor recurrence/progression, as well as time-to-event (TTE) for each of these. Participants without information on these outcome measures were excluded. Cox regression survival analyses were performed to determine predictors of mortality and tumor recurrence / progression. RESULTS: We identified 98 articles and extracted individual patient data from 188 patients. The cohort consisted of 58.9% males with a median age of 7 months. The majority (68.1%) were DIGs, while 24.5% were DIAs and 7.5% were non-specific desmoplastic infantile tumors; DIAs presented more commonly in deep locations (p = 0.001), with leptomeningeal metastasis (p = 0.001), and was associated with decreased probability of gross total resection (GTR; p = 0.001). Gender, age, and tumor pathology were not statistically significant predictors of either mortality or tumor recurrence/progression. On multivariate survival analysis, GTR was a predictor of survival (HR = 0.058; p = 0.007) while leptomeningeal metastasis at presentation was a predictor of mortality (HR = 3.27; p = 0.025). Deep tumor location (HR = 2.93; p = 0.001) and chemotherapy administration (HR = 2.02; p = 0.017) were associated with tumor recurrence/progression. CONCLUSION: Our IPDMA of DIA/DIG cases reported in the literature revealed that GTR was a predictor of survival while leptomeningeal metastasis at presentation was associated with mortality. Deep tumor location and chemotherapy were associated with tumor recurrence / progression.
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- 2021
21. Novel BRAF gene fusions and activating point mutations in spindle cell sarcomas with histologic overlap with infantile fibrosarcoma
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Brandon T. Larsen, Alyaa Al-Ibraheemi, Jessica L. Davis, Yajuan J. Liu, Tanaya Neff, Michael Michal, Karen Fritchie, Carol Beadling, Christina M. Lockwood, Soo-Jin Cho, Erin R. Rudzinski, Alyssa J. Penning, Christopher L. Corless, Vera A. Paulson, and Lukáš Plank
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,endocrine system diseases ,Point mutation ,CD34 ,Chromosomal translocation ,Biology ,digestive system diseases ,Receptor tyrosine kinase ,Pathology and Forensic Medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immunophenotyping ,Stroma ,030220 oncology & carcinogenesis ,medicine ,biology.protein ,skin and connective tissue diseases ,Infantile Fibrosarcoma ,neoplasms ,Gene - Abstract
Infantile fibrosarcoma (IFS)/cellular congenital mesoblastic nephroma (cCMN) commonly harbors the classic ETV6-NTRK3 translocation. However, there are recent reports of mesenchymal tumors with IFS-like morphology harboring fusions of other receptor tyrosine kinases or downstream effectors, including NTRK1/2/3, MET, RET, and RAF1 fusions as well as one prior series with BRAF fusions. Discovery of these additional molecular drivers contributes to a more integrated diagnostic approach and presents important targets for therapy. Here we report the clinicopathologic and molecular features of 14 BRAF-altered tumors, of which 5 had BRAF point mutations and 10 harbored one or more BRAF fusions. Of the BRAF fusion-positive tumors, one harbored two BRAF fusions (FOXN3-BRAF, TRIP11-BRAF) and another harbored three unique alternative splice variants of EPB41L2-BRAF. Tumors occurred in ten males and four females, aged from birth to 32 years (median 6 months). Twelve were soft tissue based; two were visceral including one located in the kidney (cCMN). All neoplasms demonstrated ovoid to short spindle cells most frequently arranged haphazardly or in intersecting fascicles, often with collagenized stroma and a chronic inflammatory infiltrate. No specific immunophenotype was observed; expression of CD34, S100, and SMA was variable. To date, this is the largest cohort of BRAF-altered spindle cell neoplasms with IFS-like morphology, including not only seven novel BRAF fusion partners but also the first description of oncogenic BRAF point mutations in these tumors.
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- 2021
22. Reply to Letter to the Editor: On telemedicine in rheumatology as described by Lockwood et al: A pedagogical implementation from rural Oklahoma
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Marcy B, Bolster, Megan M, Lockwood, Rachel S, Wallwork, Kaitlin, Lima, Anisha B, Dua, and Philip, Seo
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- 2022
23. 3-hour genome sequencing and targeted analysis to rapidly assess genetic risk
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Miranda Galey, Paxton Reed, Tara Wenger, Erika Beckman, Irene J. Chang, Cate R. Paschal, Jillian G. Buchan, Christina M. Lockwood, Mihai Puia-Dumitrescu, Daniel R. Garalde, Joseph Guillory, Androo J. Markham, Andrew B. Stergachis, Michael J. Bamshad, Evan E. Eichler, and Danny E. Miller
- Abstract
Rapid genetic testing in the critical care setting enables targeted evaluations, directs therapies, and helps families and care providers make informed decisions about goals of care. We tested whether we could perform ultra-rapid assessment of genetic risk for a Mendelian condition, based on information from an affected sibling, in a newborn via whole-genome sequencing using the Oxford Nanopore platform. By optimization of the DNA extraction and library preparation steps paired with targeted analysis, we were able to demonstrate within three hours of birth that the newborn was neither affected nor a carrier for variants underlying acrodermatitis enteropathica. This proof-of-concept experiment demonstrates how prior knowledge of familial variants can be used to rapidly evaluate an individual at-risk for a genetic disease.
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- 2022
24. SARS-CoV-2 Screening Testing in Schools: A Comparison of School- Vs. Home-Based Collection Methods
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Erin Chung, Ariana Magedson, Anne Emanuels, Kyle Luiten, Brian Pfau, Melissa Truong, Eric J Chow, James P Hughes, Timothy M Uyeki, Janet A Englund, Deborah A Nickerson, Christina M Lockwood, Jay Shendure, Lea M Starita, and Helen Y Chu
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Infectious Diseases ,Schools ,SARS-CoV-2 ,Pediatrics, Perinatology and Child Health ,Humans ,COVID-19 ,General Medicine - Abstract
We implemented a voluntary SARS-CoV-2 screening testing study for kindergarten-2nd grade students in a Washington School district. Weekly SARS-CoV-2 testing participation was higher for students with staff-collected nasal swabs at school than for students with parent-collected swabs at home.
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- 2022
25. Genomic surveillance of SARS-CoV-2 Omicron variants on a university campus
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Ana A. Weil, Kyle G. Luiten, Amanda M. Casto, Julia C. Bennett, Jessica O’Hanlon, Peter D. Han, Luis S. Gamboa, Evan McDermot, Melissa Truong, Geoffrey S. Gottlieb, Zack Acker, Caitlin R. Wolf, Ariana Magedson, Eric J. Chow, Natalie K. Lo, Lincoln C. Pothan, Devon McDonald, Tessa C. Wright, Kathryn M. McCaffrey, Marlin D. Figgins, Janet A. Englund, Michael Boeckh, Christina M. Lockwood, Deborah A. Nickerson, Jay Shendure, Trevor Bedford, James P. Hughes, Lea M. Starita, and Helen Y. Chu
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Multidisciplinary ,Universities ,SARS-CoV-2 ,COVID-19 ,Humans ,RNA, Viral ,General Physics and Astronomy ,Genome, Viral ,Genomics ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology - Abstract
Novel variants continue to emerge in the SARS-CoV-2 pandemic. University testing programs may provide timely epidemiologic and genomic surveillance data to inform public health responses. We conducted testing from September 2021 to February 2022 in a university population under vaccination and indoor mask mandates. A total of 3,048 of 24,393 individuals tested positive for SARS-CoV-2 by RT-PCR; whole genome sequencing identified 209 Delta and 1,730 Omicron genomes of the 1,939 total sequenced. Compared to Delta, Omicron had a shorter median serial interval between genetically identical, symptomatic infections within households (2 versus 6 days, P = 0.021). Omicron also demonstrated a greater peak reproductive number (2.4 versus 1.8), and a 1.07 (95% confidence interval: 0.58, 1.57; P
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- 2022
26. 2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases
- Author
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Anne R. Bass, Eliza Chakravarty, Elie A. Akl, Clifton O. Bingham, Leonard Calabrese, Laura C. Cappelli, Sindhu R. Johnson, Lisa F. Imundo, Kevin L. Winthrop, Reuben J. Arasaratnam, Lindsey R. Baden, Roberta Berard, S. Louis Bridges, Jonathan T. L. Cheah, Jeffrey R. Curtis, Polly J. Ferguson, Ida Hakkarinen, Karen B. Onel, Grayson Schultz, Vidya Sivaraman, Benjamin J. Smith, Jeffrey A. Sparks, Tiphanie P. Vogel, Eleanor Anderson Williams, Cassandra Calabrese, Joanne S. Cunha, Joann Fontanarosa, Miriah C. Gillispie‐Taylor, Elena Gkrouzman, Priyanka Iyer, Kimberly S. Lakin, Alexandra Legge, Mindy S. Lo, Megan M. Lockwood, Rebecca E. Sadun, Namrata Singh, Nancy Sullivan, Herman Tam, Marat Turgunbaev, Amy S. Turner, and James Reston
- Subjects
Rheumatology ,Immunology ,Immunology and Allergy ,Article - Abstract
OBJECTIVE. To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs). METHODS. This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation. RESULTS. This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence. CONCLUSION. Application of these recommendations should consider patients’ individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings.
- Published
- 2022
27. Call for improvement in medical school training in genetics: results of a national survey
- Author
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Richard L. Haspel, Jonathan R. Genzen, Jay Wagner, Karen Fong, Rebecca Wilcox, Patricia V. Adem, Hana Anderson, James B. Atkinson, Leah W. Burke, Loren Joseph, Robin D. LeGallo, Madelyn Lew, Christina M. Lockwood, Rizwan Naeem, Hasan Rizvi, Julian Sanz Ortega, Kate Shane-Carson, Mark E. Sobel, Eric Suarez, Laura J. Tafe, Jason Wang, and Rebecca L. Wilcox
- Subjects
Genetics ,media_common.quotation_subject ,education ,Needs assessment ,Medical school ,In patient ,Quality (business) ,Geneticist ,Psychology ,Training (civil) ,Genetics (clinical) ,Call to action ,media_common - Abstract
Purpose To assess, from the student perspective, medical school training in genetics and genomics. Methods In 2019, the Undergraduate Training in Genomics (UTRIG) Working Group developed genetics-related survey and knowledge questions for the RISE-FIRST, an exam administered to postgraduate year 1 (PGY1) pathology residents in the United States during their first months of training. Survey questions focused on perceived knowledge in genetics and the structure and quality of training with responses compared with those in control areas. Results There were 401 PGY1 pathology residents who took the 2019 RISE-FIRST (65% of those in the United States). There was significantly lower perceived understanding of genetics compared with nongenetics topics. Respondents also reported less time spent learning genetics and lower quality training compared with control areas. Only 53% indicated an interaction during medical school with a medical geneticist. Residents also did not perform as well on the UTRIG-developed knowledge questions than those in other areas of pathology. Conclusion The RISE-FIRST is a useful tool in assessing the current state of medical school training in genetics. This needs assessment may serve as a call to action to improve medical school genetics education and promote greater understanding of the role of genetics professionals in patient care.
- Published
- 2021
28. Reply
- Author
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Marcy B. Bolster, Megan M. Lockwood, Rachel S. Wallwork, Philip Seo, Kaitlin Lima, and Anisha B. Dua
- Subjects
Rheumatology - Published
- 2023
29. It's VALID, but Is It Rational?
- Author
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Patricia M Jones, Dennis J Dietzen, Andrew N Hoofnagle, Christina M Lockwood, Carmen L Wiley, and Eric Q Konnick
- Subjects
General Medicine - Published
- 2022
30. Novel Energy Drink Improves Cognitive Function and Gaming Performance in Young Adult Gamers: A Randomized, Double‐Blind, Placebo‐Controlled, Crossover Trial
- Author
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Laura E. Schwager, Nathaniel J. Helwig, Emily M. Rogers, Nile F. Banks, Justin P. Alpers, Sydni L. Schulte, Christopher M. Lockwood, and Nathaniel D. Jenkins
- Subjects
Genetics ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2022
31. Developing a 'Sepsis Never Event' Measure for Our Hospital-wide Improvement Initiative
- Author
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Elise Rolison, Carter Smith, Beth Wathen, Halden Scott, Sarah Nickels, and Justin M. Lockwood
- Subjects
Building and Construction - Published
- 2023
32. Re: Letter to the editor ‘risk of urinary tract infection in patients with hydroureter: An analysis from the society of fetal urology prenatal hydronephrosis registry’
- Author
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Sarah A. Holzman, Luis H. Braga, Rebecca S. Zee, C.D. Anthony Herndon, Carol A. Davis-Dao, Nora G. Kern, Joshua D. Chamberlin, Melissa McGrath, Kai-Wen Chuang, Heidi A. Stephany, Elias J. Wehbi, Tiffany T. Nguyen, Anne G. Dudley, Valre W. Welch, Gina M. Lockwood, Walid A. Farhat, and Antoine E. Khoury
- Subjects
Pregnancy ,Urology ,Urinary Tract Infections ,Pediatrics, Perinatology and Child Health ,Humans ,Female ,Hydronephrosis ,Registries ,Ultrasonography, Prenatal - Published
- 2022
33. Mapping the emergence of SARS-CoV-2 Omicron variants on a university campus
- Author
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Ana A. Weil, Kyle G. Luiten, Amanda M. Casto, Julia C. Bennett, Jessica O’Hanlon, Peter D. Han, Luis Gamboa, Evan McDermot, Melissa Truong, Geoffrey S. Gottlieb, Zack Acker, Caitlin R. Wolf, Ariana Magedson, Eric J. Chow, Natalie K. Lo, Lincoln C. Pothan, Devon McDonald, Tessa Wright, Kathryn McCaffrey, Marlin D. Figgins, Janet A. Englund, Michael Boeckh, Christina M. Lockwood, Deborah A. Nickerson, Jay Shendure, Trevor Bedford, James P. Hughes, Lea M. Starita, and Helen Y. Chu
- Abstract
Novel variants continue to emerge in the SARS-CoV-2 pandemic. University testing programs may provide timely epidemiologic and genomic surveillance data to inform public health responses. We conducted testing from September 2021 to February 2022 in a university population under vaccination and indoor mask mandates. A total of 3,048 of 24,393 individuals tested positive for SARS-CoV-2 by RT-PCR; whole genome sequencing identified 209 Delta and 1,730 Omicron genomes of the 1,939 total sequenced. Compared to Delta, Omicron had a shorter median serial interval between genetically identical, symptomatic infections within households (2 versus 6 days, P=0.021). Omicron also demonstrated a greater peak reproductive number (2.4 versus 1.8) and a 1.07 (95% confidence interval: 0.58, 1.57; P
- Published
- 2022
34. Profiling PI3K-AKT-MTOR variants in focal brain malformations reveals new insights for diagnostic care
- Author
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Filomena Pirozzi, Matthew Berkseth, Rylee Shear, Lorenzo Gonzalez, Andrew E Timms, Josef Sulc, Emily Pao, Nora Oyama, Francesca Forzano, Valerio Conti, Renzo Guerrini, Emily S Doherty, Sulagna C Saitta, Christina M Lockwood, Colin C Pritchard, William B Dobyns, Edward Novotny, Jason N N Wright, Russell P Saneto, Seth Friedman, Jason Hauptman, Jeffrey Ojemann, Raj P Kapur, and Ghayda M Mirzaa
- Subjects
Original Article ,Neurology (clinical) - Abstract
Focal malformations of cortical development including focal cortical dysplasia, hemimegalencephaly and megalencephaly, are a spectrum of neurodevelopmental disorders associated with brain overgrowth, cellular and architectural dysplasia, intractable epilepsy, autism and intellectual disability. Importantly, focal cortical dysplasia is the most common cause of focal intractable paediatric epilepsy. Gain and loss of function variants in the PI3K-AKT-MTOR pathway have been identified in this spectrum, with variable levels of mosaicism and tissue distribution. In this study, we performed deep molecular profiling of common PI3K-AKT-MTOR pathway variants in surgically resected tissues using droplet digital polymerase chain reaction (ddPCR), combined with analysis of key phenotype data. A total of 159 samples, including 124 brain tissue samples, were collected from 58 children with focal malformations of cortical development. We designed an ultra-sensitive and highly targeted molecular diagnostic panel using ddPCR for six mutational hotspots in three PI3K-AKT-MTOR pathway genes, namely PIK3CA (p.E542K, p.E545K, p.H1047R), AKT3 (p.E17K) and MTOR (p.S2215F, p.S2215Y). We quantified the level of mosaicism across all samples and correlated genotypes with key clinical, neuroimaging and histopathological data. Pathogenic variants were identified in 17 individuals, with an overall molecular solve rate of 29.31%. Variant allele fractions ranged from 0.14 to 22.67% across all mutation-positive samples. Our data show that pathogenic MTOR variants are mostly associated with focal cortical dysplasia, whereas pathogenic PIK3CA variants are more frequent in hemimegalencephaly. Further, the presence of one of these hotspot mutations correlated with earlier onset of epilepsy. However, levels of mosaicism did not correlate with the severity of the cortical malformation by neuroimaging or histopathology. Importantly, we could not identify these mutational hotspots in other types of surgically resected epileptic lesions (e.g. polymicrogyria or mesial temporal sclerosis) suggesting that PI3K-AKT-MTOR mutations are specifically causal in the focal cortical dysplasia-hemimegalencephaly spectrum. Finally, our data suggest that ultra-sensitive molecular profiling of the most common PI3K-AKT-MTOR mutations by targeted sequencing droplet digital polymerase chain reaction is an effective molecular approach for these disorders with a good diagnostic yield when paired with neuroimaging and histopathology.
- Published
- 2022
35. Mutations of the DNA repair gene PNKP in a patient with microcephaly, seizures, and developmental delay (MCSZ) presenting with a high-grade brain tumor
- Author
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Bingcheng Jiang, Cameron Murray, Bonnie L. Cole, J. N. Mark Glover, Gordon K. Chan, Jean Deschenes, Rajam S. Mani, Sudip Subedi, John D. Nerva, Anthony C. Wang, Christina M. Lockwood, Heather C. Mefford, Sarah E. S. Leary, Jeffery G. Ojemann, Michael Weinfeld, and Chibawanye I. Ene
- Subjects
Male ,Phosphotransferases (Alcohol Group Acceptor) ,DNA Repair Enzymes ,Multidisciplinary ,DNA Repair ,Brain Neoplasms ,Seizures ,Child, Preschool ,Mutation ,Microcephaly ,Humans ,Child - Abstract
Polynucleotide Kinase-Phosphatase (PNKP) is a bifunctional enzyme that possesses both DNA 3′-phosphatase and DNA 5′-kinase activities, which are required for processing termini of single- and double-strand breaks generated by reactive oxygen species (ROS), ionizing radiation and topoisomerase I poisons. Even though PNKP is central to DNA repair, there have been no reports linking PNKP mutations in a Microcephaly, Seizures, and Developmental Delay (MSCZ) patient to cancer. Here, we characterized the biochemical significance of 2 germ-line point mutations in the PNKP gene of a 3-year old male with MSCZ who presented with a high-grade brain tumor (glioblastoma multiforme) within the cerebellum. Functional and biochemical studies demonstrated these PNKP mutations significantly diminished DNA kinase/phosphatase activities, altered its cellular distribution, caused defective repair of DNA single/double stranded breaks, and were associated with a higher propensity for oncogenic transformation. Our findings indicate that specific PNKP mutations may contribute to tumor initiation within susceptible cells in the CNS by limiting DNA damage repair and increasing rates of spontaneous mutations resulting in pediatric glioma associated driver mutations such as ATRX and TP53.
- Published
- 2022
36. Clinical Testing for Tumor Cell-Free DNA
- Author
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Kelly A, Devereaux, Rhona J, Souers, Jason D, Merker, Neal I, Lindeman, Rondell P, Graham, Meera R, Hameed, Patricia, Vasalos, Joel T, Moncur, Christina M, Lockwood, and Rena R, Xian
- Subjects
Article - Abstract
CONTEXT.—: Clinical testing for tumor cell-free DNA (cfDNA) has evolved rapidly, but no practice guidelines exist. OBJECTIVE.—: To summarize cfDNA laboratory practices based on self-reporting and assess preanalytical, analytical, and postanalytical trends that may influence the quality, accuracy, and consistency of cfDNA testing. DESIGN.—: Data were derived from the College of American Pathologists cfDNA proficiency testing program submitted by 101 participating laboratories from 2018 to 2019. RESULTS.—: Most laboratories performing clinical circulating tumor DNA testing are commercial/nonhospital (71.2%; 72 of 101) and international (77.2%; 78 of 101) laboratories. Commercial laboratories had higher monthly test volumes than hospital-based laboratories (median, 36 versus 7–8) and tended to have larger gene panels (median, 50 versus 11 genes) when panel-based testing was offered. The main clinical indications include therapy selection and treatment/disease monitoring. Plasma is the most commonly accepted specimen, which is predominantly collected in cell-stabilizing tubes. Equal proportions of laboratories use next-generation sequencing (NGS) and non-NGS methods to assess key genes, including EGFR, BRAF, KRAS, NRAS, and IDH1. Most laboratories reported a lower limit of detection (LLOD) of 0.5%, variant allele frequency or less, which did not differ by method, NGS or non-NGS, except for EGFR. Sixty-five percent (17 of 26) of laboratories using the FDA-approved non-NGS EGFR assay report analytical sensitivities higher than 0.5%, as compared to 15% (16 of 104) of laboratories using an alternative NGS or non-NGS method. There is also a wider range in LLODs obtained for the FDA-approved EGFR assay than nonapproved assays. CONCLUSIONS.—: These results highlight emerging practice trends and serve as a foundation to initiate future practice recommendations.
- Published
- 2022
37. Molecularly Targeted Treatments for NF1-Mutant Diffuse Intrinsic Pontine Glioma
- Author
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Christina M. Lockwood, Bonnie Cole, Hedieh Khalatbari, Jay F. Sarthy, Sarah Leary, Ralph P. Ermoian, and Nicholas A Vitanza
- Subjects
Text mining ,business.industry ,Diffuse Intrinsic Pontine Glioma ,Mutant ,Cancer research ,Brain Stem Neoplasms ,Humans ,Medicine ,General Medicine ,business - Published
- 2020
38. Whispering-Gallery Mode Lasing in Perovskite Nanocrystals Chemically Bound to Silicon Dioxide Microspheres
- Author
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Michael Price, Meiqi Gao, Kai Chen, Nathaniel J. L. K. Davis, Isabella Wagner, Jake Hardy, Keiran Lewellen, Chase Zemke-Smith, Justin M. Hodgkiss, Johan Grand, Eric C. Le Ru, and Stephanie M. Lockwood
- Subjects
Photoluminescence ,Materials science ,Silicon dioxide ,Physics::Optics ,Halide ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Condensed Matter::Materials Science ,chemistry.chemical_compound ,Physics::Atomic and Molecular Clusters ,General Materials Science ,Physics::Atomic Physics ,Physical and Theoretical Chemistry ,Perovskite (structure) ,business.industry ,Condensed Matter::Mesoscopic Systems and Quantum Hall Effect ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Nanocrystal ,chemistry ,Optoelectronics ,Whispering-gallery wave ,0210 nano-technology ,business ,Lasing threshold ,Visible spectrum - Abstract
Cesium lead halide perovskite nanocrystals exhibit high photoluminescence quantum efficiencies and tunability across the visible spectrum. This makes these crystals ideal candidates for solar panels, light-emitting diodes, lasers, and especially nanolasers. Due to the versatility of cation substitution in perovskite nanocrystals, they can be grown on amine-functionalized silicon dioxide nanoparticles, where the amine linker replaces the standard cation structure. Selectively growing luminescent nanocrystals on spherical silicon dioxide microspheres results in the opportunity to populate whispering-gallery modes in these spherical silica microspheres. In this case, the nanocrystal halide composition can be used to selectively tune the emission wavelength mode, and microsphere radius to tune the mode spacing. This silicon dioxide attachment also adds to the overall stability of the system. Through photoluminescence microscopy measurements, we show whispering gallery modes in individual perovskite-coated microspheres for CsPbBr
- Published
- 2020
39. Integration of Genomic Medicine in Pathology Resident Training
- Author
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Karen Fong, Richard L. Haspel, Jay Wagner, Jonathan R. Genzen, and Christina M. Lockwood
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Molecular pathology ,business.industry ,Resident training ,General Medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Genomic medicine ,Medicine ,Knowledge question ,business ,Residency training - Abstract
Objectives To assess current pathology resident training in genomic and molecular pathology. Methods The Training Residents in Genomics (TRIG) Working Group has developed survey questions for the pathology Resident In-Service Examination (RISE) since 2012. Responses to these questions, as well as knowledge questions, were analyzed. Results A total of 2,529 residents took the 2019 RISE. Since 2013, there has been an increase in postgraduate year 4 (PGY4) respondents indicating training in genomic medicine (58% to approximately 80%) but still less than almost 100% each year for molecular pathology. In 2019, PGY4 residents indicated less perceived knowledge and ability related to both genomic and traditional molecular pathology topics compared with control areas. Knowledge question results supported this subjective self-appraisal. Conclusions The RISE is a powerful tool for assessing the current state and also trends related to resident training in genomic pathology. The results show progress but also the need for improvement in not only genomic pathology but traditional molecular pathology training as well.
- Published
- 2020
40. Children with DIPG and high-grade glioma treated with temozolomide, irinotecan, and bevacizumab: the Seattle Children’s Hospital experience
- Author
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Ralph P. Ermoian, Richard G. Ellenbogen, Sarah Leary, Christina M. Lockwood, Nicholas A Vitanza, Samuel R. Browd, Jason S. Hauptman, Erin E. Crotty, Aimee A Sato, Nathan Millard, Vera A. Paulson, Bonnie Cole, Amy S. Lee, James M. Olson, J. Russell Geyer, and Jeffrey G. Ojemann
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,Temozolomide ,Palliative care ,Bevacizumab ,business.industry ,medicine.medical_treatment ,medicine.disease ,Irinotecan ,03 medical and health sciences ,Regimen ,0302 clinical medicine ,Neurology ,Tolerability ,030220 oncology & carcinogenesis ,Glioma ,Internal medicine ,medicine ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Introduction Beyond focal radiation, there is no consensus standard therapy for pediatric high-grade glioma (pHGG) and outcomes remain dismal. We describe the largest molecularly-characterized cohort of children with pHGG treated with a 3-drug maintenance regimen of temozolomide, irinotecan, and bevacizumab (TIB) following radiation. Methods We retrospectively reviewed 36 pediatric patients treated with TIB at Seattle Children's Hospital from 2009 to 2018 and analyzed survival using the Kaplan-Meier method. Molecular profiling was performed by targeted DNA sequencing and toxicities, steroid use, and palliative care utilization were evaluated. Results Median age at diagnosis was 10.9 years (18 months-18 years). Genetic alterations were detected in 26 genes and aligned with recognized molecular subgroups including H3 K27M-mutant (12), H3F3A G34-mutant (2), IDH-mutant (4), and hypermutator profiles (4). Fifteen patients (42%) completed 12 planned cycles of maintenance. Side effects associated with chemotherapy delays or modifications included thrombocytopenia (28%) and nausea/vomiting (19%), with temozolomide dosing most frequently modified. Median event-free survival (EFS) and overall survival (OS) was 16.2 and 20.1 months, with shorter survival seen in DIPG (9.3 and 13.3 months, respectively). Survival at 1, 2, and 5 years was 80%, 10% and 0% for DIPG and 85%, 38%, and 16% for other pHGG. Conclusion Our single-center experience demonstrates tolerability of this 3-drug regimen, with prolonged survival in DIPG compared to historical single-agent temozolomide. pHGG survival was comparable to analogous 3-drug regimens and superior to historical agents; however, cure was rare. Children with pHGG remain excellent candidates for the study of novel therapeutics combined with standard therapy.
- Published
- 2020
41. Rainbow Darter ( Etheostoma caeruleum , Storer, 1845) predation on early ontogenetic stages of Lake Sturgeon ( Acipenser fulvescens , Rafinesque, 1817)
- Author
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Andrew M. Lockwood, Kadie B. Heinle, Kim T. Scribner, Douglas L. Larson, and Edward A. Baker
- Subjects
0106 biological sciences ,biology ,010604 marine biology & hydrobiology ,Zoology ,04 agricultural and veterinary sciences ,Aquatic Science ,biology.organism_classification ,01 natural sciences ,Substrate (marine biology) ,Predation ,Etheostoma ,Rainbow darter ,Sturgeon ,040102 fisheries ,0401 agriculture, forestry, and fisheries ,Acipenser ,Lake sturgeon ,Egg incubation - Abstract
Previous molecular diet analysis identified lake sturgeon (Acipenser fulvescens, Rafinesque, 1817) DNA in the gastrointestinal tracts of stream‐resident rainbow darters (Etheostoma caeruleum, Storer, 1845) during the egg incubation, free embryo, and larval drift stages. The objectives of this experimental study were to: (a) quantify levels of predation by rainbow darters on lake sturgeon at the egg and free‐embryo stages; and (b) evaluate whether predation varied as a function of substrate size and rainbow darter body size. We conducted experimental trials in 23‐L polycarbonate tanks 0.41 m (L) × 0.33 m (W) × 0.30 m (D) with a standardized benthic area of 0.14 m². The tanks were randomly assigned one of two different substrate size classes: large rock (51.35 mm ± 0.91 mm) or small rock (27.68 mm ± 0.57 mm). We stocked individual rainbow darter, which were deprived of feed for 48 hr, with lake sturgeon (133 individuals/m²) in each of 12 replicates per ontogenetic stage and substrate type. The number of surviving lake sturgeon was quantified following a 24‐hr predation exposure period. We used a generalized linear model with a binomial distribution to assess the influence of ontogenetic stage, substrate size, and rainbow darter body size on proportional lake sturgeon survival. Predation on lake sturgeon occurred at both egg (6.25 ± 1.16 individuals, mean ± 2SE) and free embryo (3.08 ± 1.08 individuals, mean ± 2SE) stages. Egg proportional survival was generally lower than at the free embryo stage in both substrate sizes; however, free embryo proportional survival was greater in small substrate trials. Rainbow darter total length did not affect the probability of lake sturgeon survival at either developmental stage. Results demonstrate that rainbow darters prey on early ontogenetic stages of lake sturgeon, corroborating previous results based on genetic diet analysis. Results fill a major knowledge gap concerning the vulnerability of pre‐drift sturgeon to predation by an abundant river resident species that was previously discounted as a predator for early ontogenetic stages of lake sturgeon due to its small body size.
- Published
- 2020
42. Disability Rights Monitoring: Focus on the Sustainable Development Goals
- Author
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Elizabeth M. Lockwood
- Published
- 2022
43. Key Drivers Associated with Effective Sepsis Care on a Surgical Unit
- Author
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Richele Koehler, Meghan Burke, Elise Rolison, Jennifer Newman, and Justin M Lockwood
- Subjects
Building and Construction - Published
- 2023
44. Increased Frequency of Heterozygous Alpha‐1‐Antitrypsin Deficiency in Liver Explants From Nonalcoholic Steatohepatitis Patients
- Author
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Maria Westerhoff, Charles S. Landis, Paul E. Swanson, Dina N. Greene, Lincoln J. Pac, Gregory Cheeney, Purva Gopal, Christina M. Lockwood, and Eric Q. Konnick
- Subjects
medicine.medical_specialty ,Cirrhosis ,medicine.medical_treatment ,Population ,030230 surgery ,Liver transplantation ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,alpha 1-Antitrypsin Deficiency ,Internal medicine ,medicine ,Humans ,Allele ,education ,Genotyping ,Retrospective Studies ,Transplantation ,education.field_of_study ,Alpha 1-antitrypsin deficiency ,Hepatology ,business.industry ,medicine.disease ,Liver Transplantation ,Liver ,030211 gastroenterology & hepatology ,Surgery ,Histopathology ,business - Abstract
Cirrhotic explanted livers occasionally have unexpected periodic acid-Schiff-diastase (PASD)-positive globules within the hepatocyte cytoplasm. It is often unclear whether this finding is a nonspecific consequence of cirrhosis or is indicative of an underlying alpha-1-antitrypsin deficiency (A1ATD) contributing to the cirrhosis. In this study, explanted livers were retrospectively evaluated for histopathology (including PASD status with confirmatory alpha-1-antitrypsin [A1AT] immunohistochemistry [IHC]), and chart review provided etiology of liver failure and general clinical parameters. Real-time polymerase chain reaction was used to detect A1AT genotype (SERPINA1 S and Z alleles) by melting curve analysis on liver explant tissue from selected cases. Of 196 explanted livers, 21 (11%) had PASD+ globules, which were significantly enriched in patients with a clinical diagnosis of nonalcoholic steatohepatitis (NASH; 47%) compared with other causes (P
- Published
- 2019
45. Two cases of pineal anlage tumor with molecular analysis
- Author
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Kathryn P. Scherpelz, Erin E. Crotty, Vera A. Paulson, Christina M. Lockwood, Sarah E. S. Leary, Richard G. Ellenbogen, Amy Lee, Ralph P. Ermoian, Nicholas A. Vitanza, and Bonnie L. Cole
- Subjects
Chromosome Aberrations ,Male ,Brain Neoplasms ,Infant ,Supratentorial Neoplasms ,Hematology ,Pineal Gland ,Oncology ,Pediatrics, Perinatology and Child Health ,Mutation ,Humans ,Female ,Child ,Pinealoma - Abstract
Pineal anlage tumor is a rare pediatric tumor with clinical and histological features overlapping with pineoblastoma. Two patients with pineal anlage tumor, a 13-month-old female and an 11-month-old male, underwent subtotal resection, high-dose chemotherapy with autologous stem cell rescue, and radiation. Neither had tumor progression 50 months after diagnosis. The tumors underwent next-generation sequencing on a panel of 340 genes. Chromosomal copy gains and losses were present and differed between the tumors. No mutations or amplifications, including none specific to pineoblastoma, were identified.
- Published
- 2021
46. The 'SEED' Study: The Feasibility of Selecting Patient-Specific Biologically Targeted Therapy with Sorafenib, Everolimus, Erlotinib or Dasatinib for Pediatric and Young Adult Patients with Recurrent or Refractory Brain Tumors
- Author
-
Sarah E. S. Leary, Christina M. Lockwood, Kimberly Starr, and Bonnie L. Cole
- Subjects
General Immunology and Microbiology ,Brain Neoplasms ,Patient Selection ,Dasatinib ,General Medicine ,Sorafenib ,General Biochemistry, Genetics and Molecular Biology ,Erlotinib Hydrochloride ,Young Adult ,Feasibility Studies ,Humans ,Everolimus ,Prospective Studies ,Neoplasm Recurrence, Local ,Child - Abstract
Pediatric brain tumors are the leading cause of cancer death in children and represent a variety of diseases and molecular subtypes. This study sought to evaluate a rapid immunohistochemistry testing panel to aid in therapy selection at the time of malignant tumor recurrence.With IRB approval and appropriate informed consent, we conducted a single-institution prospective clinical trial of selected kinase inhibitor therapy. A laboratory-developed immunohistochemical testing panel was performed on tumor tissue, and therapy with one of four small molecule inhibitors was recommended in combination with oral chemotherapy consisting of temozolomide and etoposide.All 20 enrolled subjects were assigned to Everolimus (n = 4), Erlotinib (n = 6) or Dasatinib (n = 10); 90% (18/20) within the pre-specified 14-day feasibility time period. Only two subjects elected treatment on study, 8 received targeted treatment based on testing results either alone (n = 5) or in combination with chemotherapy (n = 3). Other subjects received chemotherapy alone (n = 7), surgery alone (n = 2) or no further therapy (n = 3). Immunohistochemical targets were associated with correlative genetic changes in 28% (5/18) of those evaluated.It was feasible to rapidly select targeted therapy in recurrent pediatric brain tumors, but not feasible to treat with a uniform combination treatment regimen.
- Published
- 2021
47. The Seattle Flu Study: when regulations hinder pandemic surveillance
- Author
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Michael Boeckh, Helen Y. Chu, Janet A. Englund, Christina M. Lockwood, Deborah A. Nickerson, Jay Shendure, and Lea Starita
- Subjects
Washington ,SARS-CoV-2 ,Population Surveillance ,COVID-19 ,Humans ,General Medicine ,Pandemics ,General Biochemistry, Genetics and Molecular Biology - Published
- 2021
48. Most Frequently Cited Accreditation Inspection Deficiencies for Clinical Molecular Oncology Testing Laboratories and Opportunities for Improvement
- Author
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Nikoletta Sidiropoulos, Sarah K. Daley, Marian Briggs, Helen Fernandes, Christina M. Lockwood, Amer Z. Mahmoud, Jason D. Merker, Patricia Vasalos, Lynnette M. Wielgos, Joel T. Moncur, and Daniel H. Farkas
- Subjects
Medical Laboratory Technology ,education ,Humans ,General Medicine ,Clinical Laboratory Services ,Laboratories ,Medical Oncology ,Societies, Medical ,Pathology and Forensic Medicine ,Accreditation - Abstract
Context.— The College of American Pathologists (CAP), a laboratory accreditation organization with deemed status under the Clinical Laboratories Improvement Amendments of 1988 administers accreditation checklists. Checklists are used by laboratories to ensure regulatory compliance. Peer-level laboratory professionals audit laboratory records during inspections to assess compliance. Objective.— To identify the most frequently cited deficiencies for molecular oncology laboratories undergoing CAP accreditation inspections and describe laboratory improvement opportunities. Design.— The CAP Molecular Oncology Committee (MOC), which is involved in maintaining the Molecular Pathology checklist, reviewed data and inspector comments associated with the most frequently observed citations related to molecular oncology testing from laboratories inspected by the CAP during a 2-year period (2018–2020). Results.— Of 422 molecular oncology laboratories that underwent accreditation inspections, 159 (37.7%) were not cited for any molecular oncology–related deficiencies. For the All Common (COM) and Molecular Pathology checklists, there were 364 and 305 deficiencies, corresponding to compliance rates of 98.8% and 99.6%, respectively. The most frequently cited deficiencies are described. The COM checklist deficiencies were associated most often with the analytic testing phase; the MOL checklist deficiencies were more evenly distributed across the preanalytic, analytic, and postanalytic phases of testing. Conclusions.— Molecular oncology laboratories demonstrated excellent compliance with practices that support high-quality results for patients and the health care providers who use those test results in patient management. This review includes a critical assessment of opportunities for laboratories to improve compliance and molecular oncology testing quality.
- Published
- 2021
49. Multiple Copy Number Variants Detected by Noninvasive Prenatal Testing
- Author
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Sarah A Paolucci, Kimberly K Ma, Vera Paulson, Vijayakrishna K Gadi, and Christina M Lockwood
- Subjects
Chromosome Aberrations ,DNA Copy Number Variations ,Pregnancy ,Noninvasive Prenatal Testing ,Prenatal Diagnosis ,Biochemistry (medical) ,Clinical Biochemistry ,Humans ,Female ,Aneuploidy - Published
- 2021
50. Decision-Making Regarding Newborn Circumcision: A Qualitative Analysis
- Author
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Allison M, Morgan, Yue-Yung, Hu, Andrea, Benin, and Gina M, Lockwood
- Subjects
Male ,Parents ,Attitude ,Circumcision, Male ,Decision Making ,Infant, Newborn ,Humans ,Mothers ,Female ,Qualitative Research - Abstract
Circumcision of newborn males is left to parental preference, as medical necessity has not been demonstrated. For medical providers seeking to help parents make decisions and provide informed consent, there is little information regarding how parents gather and process information about circumcision. This study aimed to characterize the comprehensive range of parental attitudes, gaps in knowledge, and decision-making regarding circumcision.Qualitative data was obtained from semi-structured open-ended interviews conducted during the postpartum hospitalization. Interviews were recorded, transcribed, and coded by multiple independent reviewers. A grounded theory approach was used to identify emergent themes regarding attitudes towards, sources of information about, and decision-making surrounding circumcision.Ten mothers were interviewed, of whom six planned to circumcise and four did not. Major themes emerged: the importance of cultural norms, limited yet influential discussions, and the lack of, but desire for, more knowledge. Discussions with medical providers were often limited, though when physician conversation was more extensive, provider input was highly influential. Parents lacked evidence-based knowledge of the risks and benefits of the procedure. They uniformly desire more information and counseling from their medical providers.This study affirms the importance of sociocultural factors and identified a discrepancy between parents' desire for empiric information and the counsel offered by providers, identifying a need for improved parent counseling. The qualitative themes that emerged from this work enabled the development of a comprehensive conceptual model that can be further tested to develop a decision aid for circumcision of the newborn.
- Published
- 2021
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