Publications by authors named "A Kennedy"

2,669 Publications

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Direct and Indirect Cost Savings from STI Testing, Treatment, and Counseling among Foster Youth.

Sex Transm Dis 2021 Jul 15. Epub 2021 Jul 15.

Washington University in St. Louis; Supporting Positive Opportunities with Teens Washington University in St. Louis; Brown School Washington University in St. Louis; Adolescent Medicine.

Background: Sexually transmitted infection (STI) prevention programs can decrease the economic burden of STIs. Foster youth have higher rates of STIs compared to their peers; however, information on direct costs and indirect costs averted by STI testing, treatment, and counseling among foster youth is lacking.

Methods: This study utilized data from a comprehensive medical center for foster youth over a three-year study period from July 2017 to June 2020. Direct and indirect costs averted by testing and treatment of chlamydia, gonorrhea, and syphilis, as well as HIV testing and counseling, were calculated based on formulas developed by the Centers for Disease Control and Prevention (CDC) and adjusted for inflation.

Results: Among the 316 youth who received medical services during this time, 206 were sexually active and tested for STIs and/or HIV. Among 121 positive STI tests, 64.5% (n = 78) were positive for chlamydia, 30.6% (n = 37) were positive for gonorrhea, and 5.0% (n = 6) were positive for syphilis. Treatment was provided to all. Overall, $60,049.68 in direct medical costs and $73,956.36 in indirect costs were averted.

Conclusions: Given the rates of STIs among this population as well as the economic benefit of STI treatment, it is imperative to continue to provide intensive and comprehensive, individualized sexual healthcare for foster youth. Traditional care management may miss the opportunity to prevent, identify, and treat STIs that comprehensive wraparound care can achieve. This study suggests that comprehensive wraparound care is a cost-effective way to identify, treat, and prevent STIs among foster youth.
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http://dx.doi.org/10.1097/OLQ.0000000000001511DOI Listing
July 2021

Quantifying Mechanical Abrasion of MWCNT Nanocomposites Used in 3D Printing: Influence of CNT Content on Abrasion Products and Rate of Microplastic Production.

Environ Sci Technol 2021 Jul 15. Epub 2021 Jul 15.

Department of Civil and Environmental Engineering, Duke University, Durham, North Carolina 27708, United States.

Manufactured nanomaterials (MNMs) are incorporated as "nanofillers" into consumer products to enhance properties of interest. Multiwalled carbon nanotubes (MWCNTs) are known for their unique properties and have many applications in polymers. However, the release of MWCNTs during the nanoenabled product life cycle is concerning. During the use phase, mechanical stresses can produce fragmented materials containing MNMs. The degree of MNM release, the resulting exposure to these materials, and the potential impacts of their release are active research topics. In this study, we describe methodological improvements to study the abrasion of plastics containing MNMs (nanocomposites) and report on characteristics of abrasion products produced and rates of microplastic production. The abrasion device developed for this work allows for the measurement of power inputs to determine scaled release rates. Abrasion rates for plastics used in 3D printing were found to be 0.27 g/m/s for the PETG polymer and 0.3 g/m/s for the 2% MWCNT-PETG nanocomposite. Embedded and protuberant MWCNTs appeared to impact the particle size, shape, hydrophobicity, and surface charge of the microplastics, while the inclusion of MWCNTs had a small effect on microplastic production. Measurements of power input to the abrasion process provided a basis for estimating microplastic production rates for these nanocomposites.
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http://dx.doi.org/10.1021/acs.est.0c02015DOI Listing
July 2021

Comparison of Untargeted Metabolomic Profiling vs Traditional Metabolic Screening to Identify Inborn Errors of Metabolism.

JAMA Netw Open 2021 Jul 1;4(7):e2114155. Epub 2021 Jul 1.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.

Importance: Recent advances in newborn screening (NBS) have improved the diagnosis of inborn errors of metabolism (IEMs); however, many potentially treatable IEMs are not included on NBS panels, nor are they covered in standard, first-line biochemical testing.

Objective: To examine the utility of untargeted metabolomics as a primary screening tool for IEMs by comparing the diagnostic rate of clinical metabolomics with the recommended traditional metabolic screening approach.

Design, Setting, And Participants: This cross-sectional study compares data from 4464 clinical samples received from 1483 unrelated families referred for trio testing of plasma amino acids, plasma acylcarnitine profiling, and urine organic acids (June 2014 to October 2018) and 2000 consecutive plasma samples from 1807 unrelated families (July 2014 to February 2019) received for clinical metabolomic screening at a College of American Pathologists and Clinical Laboratory Improvement Amendments-certified biochemical genetics laboratory. Data analysis was performed from September 2019 to August 2020.

Exposures: Metabolic and molecular tests performed at a genetic testing reference laboratory in the US and available clinical information for each patient were assessed to determine diagnostic rate.

Main Outcomes And Measures: The diagnostic rate of traditional metabolic screening compared with clinical metabolomic profiling was assessed in the context of expanded NBS.

Results: Of 1483 cases screened by the traditional approach, 912 patients (61.5%) were male and 1465 (98.8%) were pediatric (mean [SD] age, 4.1 [6.0] years; range, 0-65 years). A total of 19 families were identified with IEMs, resulting in a 1.3% diagnostic rate. A total of 14 IEMs were detected, including 3 conditions not included in the Recommended Uniform Screening Panel for NBS. Of the 1807 unrelated families undergoing plasma metabolomic profiling, 1059 patients (58.6%) were male, and 1665 (92.1%) were pediatric (mean [SD] age, 8.1 [10.4] years; range, 0-80 years). Screening identified 128 unique cases with IEMs, giving an overall diagnostic rate of 7.1%. In total, 70 different metabolic conditions were identified, including 49 conditions not presently included on the Recommended Uniform Screening Panel for NBS.

Conclusions And Relevance: These findings suggest that untargeted metabolomics provided a 6-fold higher diagnostic yield compared with the conventional screening approach and identified a broader spectrum of IEMs. Notably, with the expansion of NBS programs, traditional metabolic testing approaches identify few disorders beyond those covered on the NBS. These data support the capability of clinical untargeted metabolomics in screening for IEMs and suggest that broader screening approaches should be considered in the initial evaluation for metabolic disorders.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.14155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276086PMC
July 2021

Metabolic Enzyme DLST Promotes Tumor Aggression and Reveals a Vulnerability to OXPHOS Inhibition in High-Risk Neuroblastoma.

Cancer Res 2021 Jul 7. Epub 2021 Jul 7.

Departments of Pharmacology and Medicine, Boston University School of Medicine

High-risk neuroblastoma remains therapeutically challenging to treat, and the mechanisms promoting disease aggression are poorly understood. Here we show that elevated expression of dihydrolipoamide S-succinyltransferase (DLST) predicts poor treatment outcome and aggressive disease in neuroblastoma patients. DLST is an E2 component of the a-ketoglutarate (a-KG) dehydrogenase complex, which governs the entry of glutamine into the tricarboxylic acid cycle (TCA) for oxidative decarboxylation. During this irreversible step, a-KG is converted into succinyl-CoA, producing NADH for oxidative phosphorylation (OXPHOS). Utilizing a zebrafish model of MYCN-driven neuroblastoma, we demonstrate that even modest increases in DLST expression promote tumor aggression, while monoallelic dlst loss impedes disease initiation and progression. DLST depletion in human MYCN-amplified neuroblastoma cells minimally affected glutamine anaplerosis and did not alter TCA cycle metabolites other than a-KG. However, DLST loss significantly suppressed NADH production and impaired OXPHOS, leading to growth arrest and apoptosis of neuroblastoma cells. Additionally, multiple inhibitors targeting the electron transport chain, including the potent IACS-010759 that is currently in clinical testing for other cancers, efficiently reduced neuroblastoma proliferation in vitro. IACS-010759 also suppressed tumor growth in zebrafish and mouse xenograft models of high-risk neuroblastoma. Together, these results demonstrate that DLST promotes neuroblastoma aggression and unveils OXPHOS as an essential contributor to high-risk neuroblastoma.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2153DOI Listing
July 2021
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