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1.
3D Print Addit Manuf ; 11(2): 485-495, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38689910

ABSTRACT

Multimaterial additive manufacturing is expanding the design space realizable with 3D printing, yet is largely constrained to sequential deposition of each individual material. The ability to coextrude two materials and change the ratio of materials while printing would enable custom-tailored polymer composites. Here, the evolution of a dynamic material coextrusion process for additive manufacturing capable of printing any ratio between and including two neat input materials is described across 3 hot-end generations and 14 implemented design iterations. The designs evolved with increased understanding of manufacturing constraints associated with the additive manufacturing of metal components with internal flow bore diameters on the order of 2 mm and typical bore length around 50 mm. The second generation overcame this issue by partitioning the design into two pieces to locate the flow channel geometry at the interface between the components so that the details could be easily printed on the components' external surfaces. The third concept generation then focused on minimizing flow channel volume to reduce the average length when transitioning between materials by 92%. The third-generation design was also used to investigate the improvements in dimensional stability during annealing of acrylonitrile butadiene styrene (ABS) made possible by coextruding ABS with a polycarbonate (PC) core. The standard deviation of part shrinkage after annealing was 7.08% for the neat ABS but reduced to 0.24% for the coextruded ABS/PC components.

2.
LGBT Health ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38648536

ABSTRACT

Purpose: Research and lived experience demonstrate that sexual orientation and gender identity (SOGI) can change over the life course; however, little empirical work exists to understand the prevalence of such changes. To address this gap, we used data from a large nationally representative panel of adults and adolescents to assess changes in self-reported SOGI over time and identify trends by sex assigned at birth, age, race and ethnicity, and survey mode. Methods: We reviewed SOGI data collected between 2014 and 2022 for a sample of 19,469 adults and 970 adolescents. Up to eight SOGI measurements per panelist were available over the nine-year period, collected through a combination of panel recruitment and demographic refresh surveys and topic-specific surveys. Results: Among adults older than 18 years, 4.1% reported a change in sexual orientation and 3.6% reported a change in gender identity. Among teens, who are developmentally more apt to change identity, 13.5% reported a change in sexual orientation and 9.3% reported a change in gender identity. Conclusions: Findings demonstrate that SOGI can change over time, particularly for adolescents, so it is important to re-ask SOGI questions to ensure current information. We recommend re-asking SOGI questions at least every three years of adults and every two years of adolescents. Potential undercounting of sexual and gender minority (SGM) respondents decreases visibility and our ability to understand health and economic disparities affecting these populations. Improvements in SOGI measurement can help advance data quality and, ultimately, evidence-based interventions in support of SGM communities that these data help to inform.

3.
Addit Manuf ; 842024 Mar.
Article in English | MEDLINE | ID: mdl-38567361

ABSTRACT

The working curve informs resin properties and print parameters for stereolithography, digital light processing, and other photopolymer additive manufacturing (PAM) technologies. First demonstrated in 1992, the working curve measurement of cure depth vs radiant exposure of light is now a foundational measurement in the field of PAM. Despite its widespread use in industry and academia, there is no formal method or procedure for performing the working curve measurement, raising questions about the utility of reported working curve parameters. Here, an interlaboratory study (ILS) is described in which 24 individual laboratories performed a working curve measurement on an aliquot from a single batch of PAM resin. The ILS reveals that there is enormous scatter in the working curve data and the key fit parameters derived from it. The measured depth of light penetration Dp varied by as much as 7x between participants, while the critical radiant exposure for gelation Ec varied by as much as 70x. This significant scatter is attributed to a lack of common procedure, variation in light engines, epistemic uncertainties from the Jacobs equation, and the use of measurement tools with insufficient precision. The ILS findings highlight an urgent need for procedural standardization and better hardware characterization in this rapidly growing field.

4.
Nat Chem ; 16(4): 499-505, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38307994

ABSTRACT

The light-induced ultrafast switching between molecular isomers norbornadiene and quadricyclane can reversibly store and release a substantial amount of chemical energy. Prior work observed signatures of ultrafast molecular dynamics in both isomers upon ultraviolet excitation but could not follow the electronic relaxation all the way back to the ground state experimentally. Here we study the electronic relaxation of quadricyclane after exciting in the ultraviolet (201 nanometres) using time-resolved gas-phase extreme ultraviolet photoelectron spectroscopy combined with non-adiabatic molecular dynamics simulations. We identify two competing pathways by which electronically excited quadricyclane molecules relax to the electronic ground state. The fast pathway (<100 femtoseconds) is distinguished by effective coupling to valence electronic states, while the slow pathway involves initial motions across Rydberg states and takes several hundred femtoseconds. Both pathways facilitate interconversion between the two isomers, albeit on different timescales, and we predict that the branching ratio of norbornadiene/quadricyclane products immediately after returning to the electronic ground state is approximately 3:2.

6.
J Am Chem Soc ; 146(6): 4134-4143, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38317439

ABSTRACT

Identifying multiple rival reaction products and transient species formed during ultrafast photochemical reactions and determining their time-evolving relative populations are key steps toward understanding and predicting photochemical outcomes. Yet, most contemporary ultrafast studies struggle with clearly identifying and quantifying competing molecular structures/species among the emerging reaction products. Here, we show that mega-electronvolt ultrafast electron diffraction in combination with ab initio molecular dynamics calculations offer a powerful route to determining time-resolved populations of the various isomeric products formed after UV (266 nm) excitation of the five-membered heterocyclic molecule 2(5H)-thiophenone. This strategy provides experimental validation of the predicted high (∼50%) yield of an episulfide isomer containing a strained three-membered ring within ∼1 ps of photoexcitation and highlights the rapidity of interconversion between the rival highly vibrationally excited photoproducts in their ground electronic state.

7.
Am J Cardiol ; 215: 78-79, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38185439
9.
Mol Imaging Biol ; 26(1): 124-137, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37530966

ABSTRACT

PURPOSE: Vascular endothelium plays a central role in the pathogenesis of acute and chronic radiation injuries, yet the mechanisms which promote sustained endothelial dysfunction and contribute to late responding organ failure are unclear. We employed 2nd window (> 1100 nm emission) Near-Infrared (NIR) imaging using indocyanine green (ICG) to track and define the role of the notch ligand Delta-like ligand 4 (Dll4) in mediating vascular injury in two late-responding radiosensitive organs: the lung and kidney. PROCEDURES: Consomic strains of female Salt Sensitive or SS (Dll4-high) and SS with 3rd chromosome inherited from Brown Norway, SS.BN3 (Dll4-low) rats at ages 11-12 weeks were used to demonstrate the impact of reduced Dll4 expression on long-term vascular integrity, renal function, and survival following high-dose 13 Gy partial body irradiation at 42- and 90 days post-radiation. 2nd window dynamic NIR fluorescence imaging with ICG was analyzed with physiology-based pharmacokinetic modeling and confirmed with assays of endothelial Dll4 expression to assess the role of endogenous Dll4 expression on radiation injury protection. RESULTS: We show that SS.BN3 (Dll4-low) rats are relatively protected from vascular permeability disruption compared to the SS (Dll4-high) strain. We further demonstrated that SS.BN3 (Dll4-low) rats have reduced radiation induced loss of CD31+ vascular endothelial cells, and increased Dll4 vascular expression is correlated with vascular dysfunction. CONCLUSIONS: Together, these data suggest Dll4 plays a key role in pathogenesis of radiation-induced vascular injury to the lung and kidney.


Subject(s)
Membrane Proteins , Radiation Injuries , Vascular System Injuries , Rats , Female , Animals , Endothelial Cells/metabolism , Vascular System Injuries/diagnostic imaging , Vascular System Injuries/metabolism , Intracellular Signaling Peptides and Proteins/metabolism
10.
Am J Cardiol ; 212: 141-142, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38103767
11.
J Immunol Res ; 2023: 9943584, 2023.
Article in English | MEDLINE | ID: mdl-37901346

ABSTRACT

Introduction: Elevated neutrophil counts in blood, sputum, or lung have been associated with poor clinical outcomes and more severe disease in patients with type 2 asthma. In the phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add-on dupilumab 200 and 300 mg every 2 weeks compared with matched placebo significantly reduced severe asthma exacerbations and improved forced expiratory volume in 1 s (FEV1) in patients with uncontrolled, moderate-to-severe asthma. This post hoc analysis explored the efficacy of dupilumab in patients with type 2 asthma enrolled in QUEST with or without elevated blood neutrophil counts. Methods: Annualized severe exacerbation rates during the 52-week treatment period and least-squares mean change from baseline in FEV1 over time were evaluated for patients with elevated type 2 biomarkers at baseline (blood eosinophils ≥ 150 cells/µL or fractional exhaled nitric oxide (FeNO) ≥ 20 ppb; and eosinophils ≥ 300 cells/µL or FeNO ≥ 50 ppb) and low (<4,000 cells/µL) or high (≥4,000 cells/µL) neutrophil counts. Results: Dupilumab significantly reduced annualized severe exacerbation rates compared with placebo during the 52-week treatment period in patients with elevated type 2 biomarkers, irrespective of baseline neutrophil count (P < 0.0001 for all comparisons). Significant improvements in FEV1 versus placebo were observed as early as Week 2 and over the 52-week treatment period, irrespective of baseline neutrophil count (P < 0.001 for all comparisons). Safety findings were similar across all subgroups, regardless of neutrophil counts at baseline. Conclusions: Dupilumab treatment significantly reduced annualized severe exacerbation rates and improved lung function in patients with uncontrolled, moderate-to-severe, type 2 asthma, irrespective of baseline blood neutrophil count. This trial is registered with NCT02414854.


Subject(s)
Anti-Asthmatic Agents , Asthma , Humans , Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Biomarkers , Double-Blind Method , Neutrophils
12.
Soft Matter ; 19(37): 7172-7183, 2023 Sep 27.
Article in English | MEDLINE | ID: mdl-37702523

ABSTRACT

Digital light processing (DLP)-based additive manufacturing has emerged as a powerful technique for fabricating structures from filled resin systems, in which the light scattering behavior is critical to the dimensional fidelity of the cured part. Recently created low density filled resins that incorporate hollow microspheres introduce a third optically active phase, producing yet more complex scattering and cure behaviours that existing empirical relationships cannot predict. This study simulates light scattering in these systems via Mie theory and a novel Monte Carlo model, providing insight into the relationship between filler volume fraction and cured dimensions, and proposes an inversion parameter for predicting film dimensions. Cured resin geometry dimensions such as cured depth (CD) and cured width (CW) are predicted using the developed model for 10, 30, and 50 vol% hollow glass microsphere filled resin systems. In contrast to standard two-phase models, our three-phase model predicts a positive relationship between cured depths and half-widths and the filler volume fraction, consistent with experimental data. By elucidating the intricacies of light scattering in three-phase systems, this work provides valuable insights for advancing DLP-based additive manufacturing and designing filled resin formulations to achieve the desired cured dimensions.

13.
JAMA Dermatol ; 159(11): 1185-1194, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37703003

ABSTRACT

Importance: Autoimmune bullous diseases (AIBDs) are chronic relapsing-remitting conditions with significant morbidity. Skin-related quality of life (SRQL) may vary by AIBD subtype and disease type. Disease severity and flare severity can be difficult to define; SRQL can offer a key insight. Objectives: To investigate the Skindex-16 score as an SRQL measure in AIBD subtypes during flare and nonflare states and to evaluate Skindex-16 construct validity. Design, Setting, and Participants: This retrospective cross-sectional study was conducted from September 1, 2016, to February 1, 2020, among 192 patients at the University of Utah Health autoimmune dermatology clinic with pemphigoid, pemphigus, dermatitis herpetiformis, and linear immunoglobulin A disease. Patients had an encounter-associated diagnosis, Skindex-16 scores, and self-reported flare status. Statistical analysis was performed from March 2022 to June 2023. Exposure: Autoimmune bullous disease subtype and patient-reported flare status. Main Outcomes and Measures: Skindex-16 domain scores (emotions, symptoms, and functioning; range, 0-100, where 0 indicates no effect on SRQL and 100 maximum effect) and individual item scores were described by disease and flare status. Flare scores were expected to be higher by at least the standard error of measurement (SEm). Convergent validity was assessed using Spearman correlation among Skindex-16 scores, serologic titers, and other patient-reported outcome measures. Floor or ceiling domain scores (<20% of sample scoring either lowest or highest possible domain scores, respectively) were assessed for Skindex-16. Structural validity was assessed using confirmatory factor analysis (CFA). Results: The study included 192 patients with 212 visits (median age, 68 years [IQR, 58-76 years]; 123 of 212 women [58.0%]) with Skindex-16 scores (64 in flare state and 148 in nonflare state). Median Skindex-16 domain scores were higher for all disease categories among patients in the flare state compared with those in the nonflare state (pemphigoid [emotions: flare, 52.4 (IQR, 38.1-69.0); nonflare, 7 (IQR, 0-17); symptoms: flare, 37.5 (IQR, 29.2-58.0); nonflare, 13 (IQR, 0-25); functioning: flare, 26.7 (IQR, 10.0-56.7); nonflare, 0 (IQR, 0-3)]; pemphigus [emotions: flare, 54.8 (IQR, 31.0-81.0; nonflare, 0 (IQR, 0-19); symptoms: flare, 58.3 (IQR, 41.7-70.8); nonflare, 4 (IQR, 0-12.5); functioning: flare, 26.7 (IQR, 13.3-83.3); nonflare, 0 (IQR, 0-3.33)]; dermatitis herpetiformis [emotions: flare, 72.6 (IQR, 34.7-90.5); nonflare, 14.3 (IQR, 2.4-26.2); symptoms: flare, 69 (IQR, 31.3-85.4); nonflare, 12.5 (IQR, 0-29.2); functioning: flare, 38.3 (IQR, 5.0-63.2); nonflare, 0 (IQR, 0-13.3)]. This difference exceeded SEm cut points. Cronbach α was greater than 0.80 for all domains and AIBDs. Moderate or low correlations were seen with desmoglein 1 and bullous pemphigoid 180 titers. Moderate correlation existed between Skindex-16 and Patient-Reported Outcomes Measurement Information System Depression scores (emotions: ρ = 0.40; symptoms: ρ = 0.41; functioning: ρ = 0.48), and strong correlation existed between Skindex-16 and patient-reported disease severity (emotions: ρ = 0.71; symptoms: ρ = 0.73; functioning: ρ = 0.66). Floor domain scores greater than 20% were seen among patients in the nonflare state, but ceiling domain scores were rare (<10% for all domains); CFA model fit was poor. Conclusions and Relevance: In this cross-sectional study, SRQL was highly associated with flare of AIBDs. Skin-related quality of life was worse during periods without flare among patients with pemphigoid and dermatitis herpetiformis compared with pemphigus, highlighting residual SRQL morbidity. Skindex-16 showed good construct validity, but the poor CFA model fit needs further research. Clinical measurement of SRQL in AIBDs can add critical disease-severity information.


Subject(s)
Autoimmune Diseases , Dermatitis Herpetiformis , Pemphigoid, Bullous , Pemphigus , Skin Diseases, Vesiculobullous , Humans , Female , Aged , Pemphigus/diagnosis , Quality of Life , Pemphigoid, Bullous/diagnosis , Retrospective Studies , Cross-Sectional Studies , Autoimmune Diseases/diagnosis , Skin Diseases, Vesiculobullous/diagnosis , Disease Progression
14.
Pharmacol Res ; 195: 106876, 2023 09.
Article in English | MEDLINE | ID: mdl-37536638

ABSTRACT

There is a lack of FDA-approved tocolytics for the management of preterm labor (PL). In prior drug discovery efforts, we identified mundulone and mundulone acetate (MA) as inhibitors of in vitro intracellular Ca2+-regulated myometrial contractility. In this study, we probed the tocolytic potential of these compounds using human myometrial samples and a mouse model of preterm birth. In a phenotypic assay, mundulone displayed greater efficacy, while MA showed greater potency and uterine-selectivity in the inhibition of intracellular-Ca2+ mobilization. Cell viability assays revealed that MA was significantly less cytotoxic. Organ bath and vessel myography studies showed that only mundulone exerted inhibition of myometrial contractions and that neither compounds affected vasoreactivity of ductus arteriosus. A high-throughput combination screen identified that mundulone exhibits synergism with two clinical-tocolytics (atosiban and nifedipine), and MA displayed synergistic efficacy with nifedipine. Of these combinations, mundulone+atosiban demonstrated a significant improvement in the in vitro therapeutic index compared to mundulone alone. The ex vivo and in vivo synergism of mundulone+atosiban was substantiated, yielding greater tocolytic efficacy and potency on myometrial tissue and reduced preterm birth rates in a mouse model of PL compared to each single agent. Treatment with mundulone after mifepristone administration dose-dependently delayed the timing of delivery. Importantly, mundulone+atosiban permitted long-term management of PL, allowing 71% dams to deliver viable pups at term (>day 19, 4-5 days post-mifepristone exposure) without visible maternal and fetal consequences. Collectively, these studies provide a strong foundation for the development of mundulone as a single or combination tocolytic for management of PL.


Subject(s)
Biological Products , Obstetric Labor, Premature , Premature Birth , Tocolytic Agents , Female , Infant, Newborn , Mice , Animals , Humans , Tocolytic Agents/pharmacology , Tocolytic Agents/therapeutic use , Premature Birth/drug therapy , Nifedipine/pharmacology , Nifedipine/therapeutic use , Mifepristone/therapeutic use , Biological Products/therapeutic use , Obstetric Labor, Premature/drug therapy
15.
Oral Oncol ; 144: 106487, 2023 09.
Article in English | MEDLINE | ID: mdl-37423200

ABSTRACT

OBJECTIVES: Human Papillomavirus (HPV)-negative head and neck cancer (HNC) is an aggressive malignancy with a poor prognosis. To improve outcomes, we developed a novel liposomal targeting system embedded with 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), a chlorin-based photosensitizer. Upon exposure to 660 nm light, HPPH phototriggering generates reactive oxygen species. The objective of this study was to evaluate biodistribution and test efficacy of HPPH-liposomal therapy in a patient-derived xenograft (PDX) model of chemoradioresistant HNC. MATERIALS AND METHODS: PDX models were developed from two surgically resected HNCs (P033 and P038) recurrent after chemoradiation. HPPH-liposomes were created including trace amounts of DiR (Ex/Em 785/830 nm), a near infrared lipid probe. Liposomes were injected via tail vein into PDX models. Biodistribution was assessed at serial timepoints in tumor and end-organs through in vivo DiR fluorescence. To evaluate efficacy, tumors were treated with a cw-diode 660 nm laser (90 mW/cm2, 5 min). This experimental arm was compared to appropriate controls, including HPPH-liposomes without laser or vehicle with laser alone. RESULTS: HPPH-liposomes delivered via tail vein exhibited selective tumor penetration, with a peak concentration at 4 h. No systemic toxicity was observed. Treatment with combined HPPH-liposomes and laser resulted in improved tumor control relative to either vehicle or laser alone. Histologically, this manifested as both increased cellular necrosis and decreased Ki-67 staining in the tumors treated with combined therapy. CONCLUSIONS: These data demonstrate tumor-specific anti-neoplastic efficacy of HPPH-liposomal treatment for HNC. Importantly, this platform can be leveraged in future studies for targeted delivery of immunotherapies which can be packaged within HPPH-liposomes.


Subject(s)
Head and Neck Neoplasms , Papillomavirus Infections , Photochemotherapy , Humans , Photochemotherapy/methods , Liposomes , Tissue Distribution , Papillomavirus Infections/drug therapy , Photosensitizing Agents/therapeutic use , Head and Neck Neoplasms/drug therapy
16.
Technol Cancer Res Treat ; 22: 15330338231189593, 2023.
Article in English | MEDLINE | ID: mdl-37469184

ABSTRACT

INTRODUCTION: Radiation therapy for head and neck squamous cell carcinoma is constrained by radiotoxicity to normal tissue. We demonstrate 100 nm theranostic nanoparticles for image-guided radiation therapy planning and enhancement in rat head and neck squamous cell carcinoma models. METHODS: PEG conjugated theranostic nanoparticles comprising of Au nanorods coated with Gadolinium oxide layers were tested for radiation therapy enhancement in 2D cultures of OSC-19-GFP-luc cells, and orthotopic tongue xenografts in male immunocompromised Salt sensitive or SS rats via both intratumoral and intravenous delivery. The radiation therapy enhancement mechanism was investigated. RESULTS: Theranostic nanoparticles demonstrated both X-ray/magnetic resonance contrast in a dose-dependent manner. Magnetic resonance images depicted optimal tumor-to-background uptake at 4 h post injection. Theranostic nanoparticle + Radiation treated rats experienced reduced tumor growth compared to controls, and reduction in lung metastasis. CONCLUSIONS: Theranostic nanoparticles enable preprocedure radiotherapy planning, as well as enhance radiation treatment efficacy for head and neck tumors.


Subject(s)
Head and Neck Neoplasms , Mouth Neoplasms , Nanoparticles , Radiotherapy, Image-Guided , Humans , Male , Rats , Animals , X-Rays , Squamous Cell Carcinoma of Head and Neck/diagnostic imaging , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Cell Line, Tumor , Magnetic Resonance Imaging/methods , Mouth Neoplasms/diagnostic imaging , Mouth Neoplasms/radiotherapy , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/radiotherapy
17.
bioRxiv ; 2023 Jun 08.
Article in English | MEDLINE | ID: mdl-37333338

ABSTRACT

Currently, there is a lack of FDA-approved tocolytics for the management of preterm labor (PL). In prior drug discovery efforts, we identified mundulone and its analog mundulone acetate (MA) as inhibitors of in vitro intracellular Ca 2+ -regulated myometrial contractility. In this study, we probed the tocolytic and therapeutic potential of these small molecules using myometrial cells and tissues obtained from patients receiving cesarean deliveries, as well as a mouse model of PL resulting in preterm birth. In a phenotypic assay, mundulone displayed greater efficacy in the inhibition of intracellular-Ca 2+ from myometrial cells; however, MA showed greater potency and uterine-selectivity, based IC 50 and E max values between myometrial cells compared to aorta vascular smooth muscle cells, a major maternal off-target site of current tocolytics. Cell viability assays revealed that MA was significantly less cytotoxic. Organ bath and vessel myography studies showed that only mundulone exerted concentration-dependent inhibition of ex vivo myometrial contractions and that neither mundulone or MA affected vasoreactivity of ductus arteriosus, a major fetal off-target of current tocolytics. A high-throughput combination screen of in vitro intracellular Ca 2+ -mobilization identified that mundulone exhibits synergism with two clinical-tocolytics (atosiban and nifedipine), and MA displayed synergistic efficacy with nifedipine. Of these synergistic combinations, mundulone + atosiban demonstrated a favorable in vitro therapeutic index (TI)=10, a substantial improvement compared to TI=0.8 for mundulone alone. The ex vivo and in vivo synergism of mundulone and atosiban was substantiated, yielding greater tocolytic efficacy and potency on isolated mouse and human myometrial tissue and reduced preterm birth rates in a mouse model of PL compared to each single agent. Treatment with mundulone 5hrs after mifepristone administration (and PL induction) dose-dependently delayed the timing of delivery. Importantly, mundulone in combination with atosiban (FR 3.7:1, 6.5mg/kg + 1.75mg/kg) permitted long-term management of PL after induction with 30 µg mifepristone, allowing 71% dams to deliver viable pups at term (> day 19, 4-5 days post-mifepristone exposure) without any visible maternal and fetal consequences. Collectively, these studies provide a strong foundation for the future development of mundulone as a stand-alone single- and/or combination-tocolytic therapy for management of PL.

18.
J Nucl Cardiol ; 30(6): 2418-2426, 2023 12.
Article in English | MEDLINE | ID: mdl-37173549

ABSTRACT

BACKGROUND: Myocardial imaging with bone agents such as Tc-99 m PYP and HMDP has assumed a central role in the evaluation of patients with suspected transthyretin (TTR) amyloidosis. Visual scoring (VS) (0-3 +) and the heart to contralateral lung ratio (HCL) classify many patients as equivocal when mediastinal uptake is apparent but cannot be further differentiated into myocardial uptake versus blood pool. SPECT imaging has been recommended but current reconstruction protocols frequently produce amorphous mediastinal activity that also fails to discriminate between myocardial activity and blood pool. We hypothesized that interactive filtering interactively using a deconvolving filter would improve this. METHODS: We identified 176 sequential patients referred for TTR amyloid imaging. All patients had planar imaging, 101 had planar imaging with a large field of view camera that allowed HCL measurements. SPECT imaging was performed on a 3-headed digital camera with lead fluorescence attenuation correction. One study was excluded for technical reasons. We created software to allow interactive filtering while reconstructing the images then overlay them on attenuation mu maps to assist localization of myocardial/mediastinal uptake. Conventional Butterworth and an interactive inverse Gaussian filters were employed to differentiate myocardial uptake from residual blood pool. We defined "clean blood pool" (CBP) as recognizable blood pool with no activity in the surrounding myocardium. A scan was determined diagnostic if it showed CBP, positive uptake or no identifiable mediastinal uptake. RESULTS: 76/175 (43%) were equivocal (1 +) by visual uptake. Of these 22 (29%) were diagnostic by Butterworth but 71 (93%) were by inverse gaussian (p < .0001). 71/101 (70%) were equivocal by HCL (1-1.5). Of these, 25 (35%) were diagnostic by Butterworth but 68 (96%) were diagnostic by inverse gaussian (p < .0001). This was driven by a greater than threefold increase in the identification of CBP by inverse gaussian filtering. CONCLUSION: CBP can be identified in the vast majority of patients with equivocal PYP scans using optimized reconstruction and can greatly reduce the number of equivocal scans.


Subject(s)
Amyloidosis , Cardiomyopathies , Humans , Technetium Tc 99m Pyrophosphate , Prealbumin , Heart , Tomography, Emission-Computed, Single-Photon , Radiopharmaceuticals
19.
Prev Sci ; 24(6): 1128-1141, 2023 08.
Article in English | MEDLINE | ID: mdl-37086334

ABSTRACT

Transgender and gender diverse (TGD) youth experience significant risk for negative health outcomes, yet few studies exist that address TGD youth's experiences of health care. This paper explores the equitable access and utilization of health care in a sample of TGD youth of diverse gender and racial/ethnic identities. Data for this analysis are from the TGD subsample (n = 1415) of the 2018 Survey of Today's Adolescent Relationships and Transitions (START) Project. We assessed five health care experiences: being insured, having a current health care provider, being out to one's provider, believing your provider was knowledgeable about transgender issues, and barriers to accessing care due to gender identity/expression. We examined the proportion of TGD youth who reported each of these outcomes and within-group differences by gender identity and race/ethnicity using descriptive statistics, logistic regression, and predicted probabilities. When differences were examined by gender identity, barriers to equitable care were consistently more present among transgender females than youth of other gender identities. There were few significant differences by race/ethnicity; however, dual referent models demonstrated barriers to equitable care were particularly evident among Black and Hispanic transgender women. We discuss these findings through the lens of intersectionality and highlight the importance of research and intervention work focused on reducing barriers to equitable care for TGD youth.


Subject(s)
Transgender Persons , Humans , Female , Male , Adolescent , Gender Identity , Ethnicity , Delivery of Health Care , Surveys and Questionnaires
20.
Chem Sci ; 14(10): 2501-2517, 2023 Mar 08.
Article in English | MEDLINE | ID: mdl-36908956

ABSTRACT

Photochemistry plays a significant role in shaping the chemical reaction network in the solar nebula and interstellar clouds. However, even in a simple triatomic molecule photodissociation, determination of all fragmentation processes is yet to be achieved. In this work, we present a comprehensive study of the photochemistry of H2S, derived from cutting-edge translational spectroscopy measurements of the H, S(1D) and S(1S) atom products formed by photolysis at wavelengths across the range 155-120 nm. The results provide detailed insights into the energy disposal in the SH(X), SH(A) and H2 co-fragments, and the atomisation routes leading to two H atoms along with S(3P) and S(1D) atoms. Theoretical calculations allow the dynamics of all fragmentation processes, especially the bimodal internal energy distributions in the diatomic products, to be rationalised in terms of non-adiabatic transitions between potential energy surfaces of both 1A' and 1A'' symmetry. The comprehensive picture of the wavelength-dependent (or vibronic state-dependent) photofragmentation behaviour of H2S will serve as a text-book example illustrating the importance of non-Born-Oppenheimer effects in molecular photochemistry, and the findings should be incorporated in future astrochemical modelling.

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