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Abstract A drug–drug interaction (DDI) study was conducted to evaluate the effect of icenticaftor (QBW251) on the pharmacokinetics (PK) of a 5‐probe cytochrome P450 (CYP) substrate cocktail, guided by in vitro studies in human hepatocytes and liver microsomes. Another DDI study investigated the effect of icenticaftor on the PK and pharmacodynamics (PD) of a monophasic oral contraceptive (OC) containing ethinyl estradiol (EE) and levonorgestrel (LVG) in premenopausal healthy female subjects. The static‐mechanistic DDI assessment indicated that icenticaftor may moderately induce the metabolic clearance of co‐medications metabolized by CYP3A4 (area under the concentration–time curve [AUC] ratio: 0.47) and potentially CYP2C; icenticaftor may also weakly inhibit the metabolic clearance of co‐medications metabolized by CYP1A2 and CYP3A4 (AUC ratio: 1.35 and 1.86, respectively) and moderately inhibit CYP2B6 (AUC ratio: 2.11). In the CYP substrate cocktail DDI study, icenticaftor 300 mg twice daily (b.i.d.) moderately inhibited CYP1A2 (AUC ratio: 3.35) and CYP2C19 (AUC ratio: 2.70). As expected from the results of the in vitro studies, weak induction was observed for CYP3A4 (AUC ratio: 0.51) and CYP2C8 (AUC ratio: 0.66). In the OC DDI study, co‐administration of icenticaftor 450 mg b.i.d. with monophasic OC containing 30‐μg EE and 150‐μg LVG once daily reduced the plasma exposure of both components by approximately 50% and led to increased levels of follicle‐stimulating hormone and luteinizing hormone. These results provide valuable guidance for the use of icenticaftor in patients taking concomitant medications that are substrates of CYP enzymes or patients using OCs.

Abstract Background Long‐term exercise induces cardiac remodeling that potentially influences the electrical properties of the heart. Hypothesis/objectives We assessed whether training alters cardiac conduction in Standardbred racehorses. Animals Two hundred one trained and 52 untrained Standardbred horses. Methods Cross‐sectional study. Resting ECG recordings were analyzed to assess heart rate (HR) along with standard ECG parameters and for identification of atrial and ventricular arrhythmias. An electrophysiological study was performed in 13 horses assessing the effect of training on sinoatrial (SA) and atrioventricular (AV) nodal function by sinus node recovery time (SNRT) and His signal recordings. Age and sex adjustments were implemented in multiple and logistic regression models for comparison. Results Resting HR in beats per minute (bpm) was lower in trained vs untrained horses (mean, 30.8 ± 2.6 bpm vs 32.9 ± 4.2 bpm; P = .001). Trained horses more often displayed second‐degree atrioventricular block (2AVB; odds ratio, 2.59; P = .04). No difference in SNRT was found between groups (n = 13). Mean P‐A, A‐H, and H‐V intervals were 71 ± 20, 209 ± 41, and 134 ± 41 ms, respectively (n = 7). We did not detect a training effect on AV‐nodal conduction intervals. His signals were present in 1 horse during 2AVB with varying H‐V interval preceding a blocked beat. Conclusions and Clinical Importance We identified decreased HR and increased frequency of 2AVB in trained horses. In 5 of 7 horses, His signal recordings had variable H‐V intervals within each individual horse, providing novel insight into AV conduction in horses.

Abstract Hawaiian volcanoes record 6 Ma of potentially deep mantle chemistry and form two parallel volcanic chains that are geochemically unique, named Loa and Kea. Loa volcanoes erupt lavas with isotopically enriched compositions thought to reflect the presence of recycled material in the deep mantle source of the Hawaiian plume. Variations in stable thallium (Tl) isotopes have been used to trace recycled pelagic ocean sediment from subduction to eruption in arc and intraplate lavas. Previous work attributed heavy Tl isotopic compositions in eight Loa samples to recycled sediments in their source. We reexamined this hypothesis using a large sample set (n = 34) of shield‐stage, tholeiitic basalt from 13 Hawaiian volcanoes representing the entire range of isotopically enriched and depleted compositions along the Hawaiian chain. Samples were acid‐leached prior to isotopic analysis to remove post‐eruption alteration and resulting ε205Tl values show statistical differences between Loa and Kea volcanoes. Corresponding isotopic data and re‐analyzed trace element concentrations suggest that the ε205Tl values are primary magmatic signatures. Possible co‐variations between heavy ε205Tl and oxygen isotopes in samples from Kea‐trend volcanoes could reflect the presence of ancient, recycled pelagic sediment on the Kea side of the Hawaiian plume, which samples the average deep Pacific mantle. As such, the deep mantle source of both Loa and Kea Hawaiian volcanoes may contain recycled materials of different natures and recycling histories, which supports work from both geophysical and geochemical studies suggesting that the Earth's lower mantle is chemically heterogeneous on multiple spatial scales.

Abstract The clastic‐dominant (CD‐type) deposits that are contained within sedimentary basins are major resources of Zn, Pb and Ag, but their formation by basin‐scale hydrothermal mass and energy transport processes is still poorly understood. Using geological constraints from the Late Devonian Selwyn Basin (Canada), we apply quantitative numerical fluid flow modeling to explore the effect of strata permeability, timing of fault opening and increased heat flow in controlling fluid migration, metal leaching and ore formation during an extensional tectonic event. The results indicate that tapping hot fluids from a confined and permeable aquifer at several km depths by means of permeable normal faults is a key factor for the formation of large Zn‐Pb deposits. The hot (282°C) ore‐forming fluids are transported to the shallow subsurface shortly after the initiation of a rifting event (within 100 kyr), before the development of extensive basin‐scale convection patterns that lead to stronger cooling and a reduction in the capacity of the hydrothermal system to make an economic deposit. Such a hydrothermal event can result in metal endowments comparable to the deposits of the Selwyn Basin.

Abstract Amphistegina are common larger benthic foraminifer in coral reefs, with a nearly circumtropical distribution, and are major contributors to the CaCO3 budget of shallow marine environments. The family Amphisteginidae is dominant in Cenozoic carbonates. However, its potential as a proxy for paleoclimate reconstruction has not been completely explored. The intratest variability in trace elements of Amphistegina lessonii has been investigated using femtosecond‐laser ablation‐inductively coupled plasma‐mass spectrometry (fs‐LA‐ICP‐MS). We collected and analyzed adult specimens of A. lessonii in September 2003, November 2003, January 2004, and March 2004, from ∼2 m water depth in the coral reefs of Akajima, Okinawa, Japan. Tests of A. lessonii from these four collections were analyzed for Mg/Ca of the septa to observe Test Size‐Lifespan relationships. The lifespan of a specimen of A. lessonii of 1,200 µm in diameter is estimated at ∼3 and ∼2 months for specimens 900 µm in size. Over the estimated lifespans, Mg/Ca of individual specimens of A. lessonii is highly variable and displays co‐variation with temperature and tidal heights. Future projects may apply and further test this approach for the reconstruction of the tropical shallow marine paleoenvironments.

Abstract Hawaiian volcanoes belong to two geographically and geochemically distinct trends, the Loa and Kea trends. The cause of this dichotomy is still strongly debated. One of the prevailing hypotheses is that the two trends originate in the deep mantle where the Hawaiian mantle plume straddles two geophysically and geochemically distinct domains at the core‐mantle boundary (CMB). New high‐precision multi‐isotopic (Pb, Hf, Nd, and Sr) compositions of lavas from three key volcanoes, Lō‘ihi, Kohala, and Haleakalā, show transitional signatures between Loa and Kea compositions that call into question the degree of physical independence between the two trends. Statistical analysis of multi‐collector inductively coupled plasma mass spectrometer or triple‐spike Pb (n > 800) and Sr, Nd, and Hf data (n > 400) for shield tholeiites from the entire Hawaiian Islands (

Abstract The Galápagos and Hawai'i archipelagos are formed by mantle plumes originating at the large low shear velocity province (LLSVP) boundary. We report new high‐precision Pb, Sr, Nd, and Hf isotopic analyses on 83 Galápagos samples and compare them with those of Hawai'i. The data confirm that like Hawai'i, Galápagos is a bilaterally asymmetric plume whose compositional boundary trends NW‐SE. On their northeast sides, the plumes share a common source, Pacific lower mantle, whose intermediate isotopic signature may be common to many plumes. The Hawaiian and Galápagos plumes' southwestern sides are anchored in the Pacific LLSVP and are compositionally distinct; in Hawai'i, Loa trend lavas reflect contributions from the EM1 mantle end‐member, whereas in Galápagos, HIMU is dominant, suggesting that the Pacific LLSVP is compositionally heterogeneous and includes different types of recycled material. Furthermore, the surficial expression of a bilaterally asymmetric plume is strongly influenced by its tectonic setting: (a) Thick Hawaiian lithosphere supports a volcano evolution process, including rejuvenated volcanism, whereas the thin Galápagos lithosphere inhibits Hawai'i‐style rejuvenated‐stage eruptive activity, instead causing extended, widespread volcanism; (b) the proximity of the Galápagos to a mid‐ocean ridge causes entrainment of the depleted upper mantle, overwhelming depleted material intrinsic to the plume and affecting volcanoes' magmatic architecture; and (c) the geometric relationship between the LLSVP boundary and plate motion influences geochemical patterns at the surface. Thus, despite striking differences in surficial expression of the Galápagos and Hawai'i plumes, they share a common generation mechanism, supplied by the Pacific LLSVP and the lower mantle.

Premise Precise pollen collection methods are necessary for crop breeding, but anemophilous pollen is notoriously difficult to capture and control. Here we compared a variety of methods for the controlled capture of cannabis pollen, intended to ease the process of cross‐fertilization for breeding this wind‐pollinated plant, and measured the utility of light spectroscopy for quantifying relative pollen yield. Methods and Results In two independent trials, we compared a control method of pollen collection (hand collection) to either vacuum‐, water‐, or bag‐collection methods. We used visible light spectroscopy to quantify relative pollen yield, and validated this approach using microscopic pollen counts. We determined that pollen yield was highest when using hand collection or vacuum collection, but efficiency did not differ significantly among methods. Conclusions To maximize yield, pollen should be collected by hand or vacuum, but all collection methods were equally efficient in a relative sense because yield increased with collection time. We also found that light spectroscopy is an accurate and rapid method of quantifying pollen abundance (R2 = 0.86) in a liquid suspension.

Abstract The Hawaiian‐Emperor chain is the ∼6,000 km long surface expression of the deeply sourced Hawaiian mantle plume active over the past ∼81 Myr. The Hawaiian Islands (81–47 Ma) show only Kea compositions. New Sr‐Nd‐Hf isotope, trace and major element data of 23 Northwest Hawaiian Ridge (∼47–6.5 Ma) shield‐stage tholeiitic basalts analyzed in this study fill a critical gap and show both Kea and Loa compositions. A logistic regression model fit to a high‐quality isotopic database of Hawaiian Island basalts is used to predict Loa‐type or Kea‐type affinity of new NWHR isotope analyses. Daikakuji, Mokumanamana, West Nīhoa, Nīhoa, and Middle Bank erupt Loa‐type compositions, a finding corroborated by their geochemical characteristics (e.g., low Th/La, CaO/Al2O3, and high Sr/Nb, Zr/Nb, SiO2). Participation of the Loa composition gradually increases toward the Hawaiian Islands with time and there is no evidence for the presence of the Lō‘ihi component along the NWHR or before ∼1 Myr. A new Hf‐Nd Hawaiian array is calculated based on an up‐to‐date extended Hawaiian Island basalt database (n = 403). The NWHR array is slightly steeper than the Hawaiian array, suggesting minimal participation of the high Hf isotopic source component present in Hawaiian Island volcanoes before ∼6.5 Ma. This study fills a significant geochemical data gap in the Hawaiian‐Emperor seamount chain, and shows that Hawaiian plume chemistry evolves significantly with time as the plume samples different deep mantle reservoirs.