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Abstract The Black Warrior foreland basin records sedimentation associated with the development of intersecting Ouachita and Alleghanian thrust belts along the southern margin of Laurentia. Mississippian–Pennsylvanian units in the Black Warrior basin are interpreted to be sourced from either the northern Appalachians and mid-continent or more regionally from the southern Appalachians or nearby Ouachita thrust belt. We present detrital zircon U-Pb ages and Th/U values from Paleozoic units that indicate zircon from the Mississippian Hartselle Sandstone are temporally and chemically compatible with being sourced from the southern Appalachians. Zircon mixing models suggest sediment was primarily recycled from Cambrian, Ordovician, and Devonian strata in the Appalachian Valley and Ridge, with minor influx from Piedmont units. A ca. 415 Ma zircon population requires additional input from the Maya Block of the Yucatan Peninsula or similar outboard terranes. We present zircon (U-Th)/He analysis and thermal history modeling of Paleozoic units, which detail pre-Alleghanian exhumation in the Appalachian Valley and Ridge. Both the Cambrian Chilhowee Group and Pennsylvanian Pottsville Formation exhibit (U-Th)/He dates ranging from 507 to 263 Ma with a Mississippian subset (353–329 Ma, n = 4), which indicates rapid cooling and inferred exhumation during Late Devonian–Early Mississippian Neoacadian tectonism. We propose a Mississippian drainage system that transported material along southern Appalachian structural fabrics to the juncture between Appalachian and Ouachita thrust belts followed by a sediment-routing rotation toward the Black Warrior foreland. This interpretation honors chemical-age zircon data, accounts for metamorphic grains in thin section petrography, and matches Mississippian–Pennsylvanian Black Warrior foreland lithostratigraphic relationships.more » « less
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Importance Continuous glucose monitoring (CGM) is associated with improvements in hemoglobin A 1c (HbA 1c ) in youths with type 1 diabetes (T1D); however, youths from minoritized racial and ethnic groups and those with public insurance face greater barriers to CGM access. Early initiation of and access to CGM may reduce disparities in CGM uptake and improve diabetes outcomes. Objective To determine whether HbA 1c decreases differed by ethnicity and insurance status among a cohort of youths newly diagnosed with T1D and provided CGM. Design, Setting, and Participants This cohort study used data from the Teamwork, Targets, Technology, and Tight Control (4T) study, a clinical research program that aims to initiate CGM within 1 month of T1D diagnosis. All youths with new-onset T1D diagnosed between July 25, 2018, and June 15, 2020, at Stanford Children’s Hospital, a single-site, freestanding children’s hospital in California, were approached to enroll in the Pilot-4T study and were followed for 12 months. Data analysis was performed and completed on June 3, 2022. Exposures All eligible participants were offered CGM within 1 month of diabetes diagnosis. Main Outcomes and Measures To assess HbA 1c change over the study period, analyses were stratified by ethnicity (Hispanic vs non-Hispanic) or insurance status (public vs private) to compare the Pilot-4T cohort with a historical cohort of 272 youths diagnosed with T1D between June 1, 2014, and December 28, 2016. Results The Pilot-4T cohort comprised 135 youths, with a median age of 9.7 years (IQR, 6.8-12.7 years) at diagnosis. There were 71 boys (52.6%) and 64 girls (47.4%). Based on self-report, participants’ race was categorized as Asian or Pacific Islander (19 [14.1%]), White (62 [45.9%]), or other race (39 [28.9%]); race was missing or not reported for 15 participants (11.1%). Participants also self-reported their ethnicity as Hispanic (29 [21.5%]) or non-Hispanic (92 [68.1%]). A total of 104 participants (77.0%) had private insurance and 31 (23.0%) had public insurance. Compared with the historical cohort, similar reductions in HbA 1c at 6, 9, and 12 months postdiagnosis were observed for Hispanic individuals (estimated difference, −0.26% [95% CI, −1.05% to 0.43%], −0.60% [−1.46% to 0.21%], and −0.15% [−1.48% to 0.80%]) and non-Hispanic individuals (estimated difference, −0.27% [95% CI, −0.62% to 0.10%], −0.50% [−0.81% to −0.11%], and −0.47% [−0.91% to 0.06%]) in the Pilot-4T cohort. Similar reductions in HbA 1c at 6, 9, and 12 months postdiagnosis were also observed for publicly insured individuals (estimated difference, −0.52% [95% CI, −1.22% to 0.15%], −0.38% [−1.26% to 0.33%], and −0.57% [−2.08% to 0.74%]) and privately insured individuals (estimated difference, −0.34% [95% CI, −0.67% to 0.03%], −0.57% [−0.85% to −0.26%], and −0.43% [−0.85% to 0.01%]) in the Pilot-4T cohort. Hispanic youths in the Pilot-4T cohort had higher HbA 1c at 6, 9, and 12 months postdiagnosis than non-Hispanic youths (estimated difference, 0.28% [95% CI, −0.46% to 0.86%], 0.63% [0.02% to 1.20%], and 1.39% [0.37% to 1.96%]), as did publicly insured youths compared with privately insured youths (estimated difference, 0.39% [95% CI, −0.23% to 0.99%], 0.95% [0.28% to 1.45%], and 1.16% [−0.09% to 2.13%]). Conclusions and Relevance The findings of this cohort study suggest that CGM initiation soon after diagnosis is associated with similar improvements in HbA 1c for Hispanic and non-Hispanic youths as well as for publicly and privately insured youths. These results further suggest that equitable access to CGM soon after T1D diagnosis may be a first step to improve HbA 1c for all youths but is unlikely to eliminate disparities entirely. Trial Registration ClinicalTrials.gov Identifier: NCT04336969more » « less
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To address biophysical principles and lipid interactions that underlie the properties of membrane proteins, modifications that vary the neighbors of tryptophan residues in the highly dynamic transmembrane helix of GW4,20ALP23 (acetyl‐GGAW4A(LA)6LAW20AGA‐amide) were examined using deuterium NMR spectroscopy. It was found that L5,19GW4,20ALP23, a sequence isomer of the low to moderately dynamic GW5,19ALP23, remains highly dynamic. By contrast, a removal of W4 to produce F4,5GW20ALP23 restores a low level of dynamic averaging, similar to that of the F4,5GW19ALP23 helix. Interestingly, a high level of dynamic averaging requires the presence of both tryptophan residues W4 and W20, on opposite faces of the helix, and does not depend on whether residue 5 is Leu or Ala. Aspects of helix unwinding and potential oligomerization are discussed with respect to helix dynamic averaging and the locations of particular residues at a phosphocholine membrane interface.more » « less
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