Structure of the moiré exciton captured by imaging its electron and hole.

Interlayer excitons (ILXs) - electron-hole pairs bound across two atomically thin layered semiconductors - have emerged as attractive platforms to study exciton condensation1-4, single-photon emission and other quantum information applications5-7. Yet, despite extensive optical spectroscopic investigations8-12, critical information about their size, valley configuration and the influence of the moiré potential remains unknown. Here, in a WSe2/MoS2 heterostructure, we captured images of the time-resolved and momentum-resolved distribution of both of the particles that bind to form the ILX: the electron and the hole. We thereby obtain a direct measurement of both the ILX diameter of around 5.2 nm, comparable with the moiré-unit-cell length of 6.1 nm, and the localization of its centre of mass. Surprisingly, this large ILX is found pinned to a region of only 1.8 nm diameter within the moiré cell, smaller than the size of the exciton itself. This high degree of localization of the ILX is backed by Bethe-Salpeter equation calculations and demonstrates that the ILX can be localized within small moiré unit cells. Unlike large moiré cells, these are uniform over large regions, allowing the formation of extended arrays of localized excitations for quantum technology.

Observation of quadrupolar and dipolar excitons in a semiconductor heterotrilayer.

Van der Waals (vdW) materials have opened up many avenues for discovery through layer assembly, as epitomized by interlayer dipolar excitons that exhibit electrically tunable luminescence, lasing and exciton condensation. Extending interlayer excitons to more vdW layers, however, raises fundamental questions concerning coherence within excitons and coupling between moiré superlattices at multiple interfaces. Here, by assembling angle-aligned WSe2/WS2/WSe2 heterotrilayers, we demonstrate the emergence of quadrupolar excitons. We confirm the exciton's quadrupolar nature by the decrease in its energy of 12 meV from coherent hole tunnelling between the two outer layers, its tunable static dipole moment under an external electric field and the reduced exciton-exciton interactions. At high exciton density, we also see signatures of a phase of oppositely aligned dipolar excitons, consistent with a staggered dipolar phase predicted to be driven by attractive dipolar interactions. Our demonstration paves the way for discovering emergent exciton orderings for three vdW layers and beyond.

Axial length and pharmacologic pupillary dilation in highly myopic patients.

PURPOSE: To determine how high myopia impacts pharmacological pupillary dilation, and to evaluate the relationship between the extent of pharmacologic pupillary dilation and axial length. METHODS: Patients were grouped into high myopes, defined as one or both eyes having a refractive error greater than - 6 diopters, and controls (between - 2 and + 2 diopters). Dilation was achieved with 1 drop each of tropicamide 1% and phenylephrine 2.5%. Pupil size was measured at full and dim light prior to dilation, then 15 and 30 min after dilation. Biometry was measured for each patient. Statistical analyses were performed using the Mann-Whitney-Wilcoxon tests, two-sample Welch's t-tests, and linear mixed effect models and generalized estimating equations models accounting for inter-eye correlation. RESULTS: Forty patients (20 high myopes and 20 controls, 80 eyes total) participated in the study. High myopes had larger pupils at baseline and achieved significantly greater pupillary size (7.08 mm, 95% CI: 6.97 to 7.19 mm) than controls (6.23 mm, 95% CI: 5.94 to 6.52 mm) after 30 min of dilation (P < .0005). Fully dilated pupil size at 30 min was significantly correlated with both refractive error (r = - 0.57, P < .0005) and axial length (r = 0.47, P < .0005). Generalized estimating equations and linear mixed effect models identified other predictive variables of pupil size after dilation including age and white-to-white diameter. CONCLUSIONS: Highly myopic patients dilate to a larger pupillary size compared to other patients. Predicting dilation based on extent of myopia could facilitate intraocular surgery planning and reduce clinic wait times for myopic patients.

Influence of Anatomic Locations of T1b Melanomas and Patient Age on Outcomes.

BACKGROUND: There are no guidelines on when to more strongly recommend sentinel lymph node biopsy (SLNB) for T1b melanomas. OBJECTIVE: To examine whether anatomic locations of T1b melanomas and patient age influence metastases. METHODS: We conducted a retrospective study using data from two hospitals in Los Angeles County from January 2010 through January 2020. RESULTS: Out of 620 patients with primary melanomas, 566 melanomas were staged based on the American Joint Committee on Cancer 8th edition melanoma staging. Forty-one were T1b, of which 13 were located on the face/ear/scalp and 28 were located elsewhere. T1b melanomas located on the face/ear/scalp had an increased risk of lymph node or distant metastasis compared with other anatomic sites (31% vs 3.6%, P=0.028). For all melanomas, the risk of lymph node or distant metastasis decreased with age of 64 years or greater (P<0.001 and P=0.034). For T1b melanomas, the risk of distant metastasis increased with increasing age (P=0.047). LIMITATIONS: Data were from a single county.  Conclusion: T1b melanomas of the face/ear/scalp demonstrated a higher risk of lymph node or distant metastasis and may help guide the recommendation of SLNB, imaging, and surveillance. Younger patients may be more strongly considered for SLNB and older patients with T1b melanomas may warrant imaging.  J Drugs Dermatol. 2024;23(5):306-310. doi:10.36849/JDD.7667.

Is Blepharoplasty Cost-effective? Utility Analysis of Dermatochalasis and Cost-effectiveness Analysis of Upper Eyelid Blepharoplasty.

PURPOSE: This cross-sectional prospective study measured utility values of upper eyelid dermatochalasis to quantify its impact on quality of life and assess cost-effectiveness of upper blepharoplasty. METHODS: Utility of dermatochalasis was assessed using the standard reference gamble and time trade-off methods, with dual anchor points of perfect eye function and perfect health. The utility value obtained was used to create a Markov model and run a cost-effectiveness analysis of blepharoplasty as a treatment for dermatochalasis while utilizing the societal perspective. RESULTS: One hundred three patients with dermatochalasis recruited from an urban outpatient ophthalmology clinic completed the utility survey. The authors determined utility values for dermatochalasis ranging from 0.74 to 0.92 depending on the measurement method (standard reference gamble/time trade-off) and anchor points. The cost-effectiveness analysis yielded an incremental cost-effectiveness ratio of $3,146 per quality-adjusted life year, well under the conventional willingness-to-pay threshold of $50,000 per quality-adjusted life year. Probabilistic sensitivity analysis with Monte Carlo simulation demonstrated that blepharoplasty would be cost-effective in 88.1% of cases at this willingness-to-pay threshold. CONCLUSIONS: Dermatochalasis has an impact on quality of life that is significantly associated with level of perceived functional impairment. Rising health care costs have underscored the importance of providing value-based treatment to patients, and the results of this study suggest that blepharoplasty is a cost-effective treatment option for symptomatic bilateral upper eyelid dermatochalasis.

Moiré-Assisted Strain Transfer in Vertical van der Waals Heterostructures.

Strain provides a powerful method to study 2D monolayers and to tune their properties. The same approach also has great potential for van-der-Waals (vdW) heterostructures. However, we need to understand how strain can be applied to vertically stacked vdW structures, for which strain transfer from one layer to the next remains little explored. In our experiment, we fabricated vertical heterostructures consisting of transition metal dichalcogenides (TMDCs) monolayers that were deposited on a flexible substrate. These TMDC heterostructures allowed us to read out separately the strain in each monolayer by photoluminescence measurements. We find that, in TMDC heterostructures with large twist angles (>5°), strain transfer is limited. However, for aligned heterostructures with small twist angles (≤5°), near unity strain transfer efficiency is observed. We correlate this finding with the moiré domains formed in the aligned heterostructures by reconstruction.

The Reststrahlen Effect in the Optically Thin Limit: A Framework for Resonant Response in Thin Media.

Sharp resonances can strongly modify the electromagnetic response of matter. A classic example is the Reststrahlen effect - high reflectivity in the mid-infrared in many polar crystals near their optical phonon resonances. Although this effect in bulk materials has been studied extensively, a systematic treatment for finite thickness remains challenging. Here we describe, experimentally and theoretically, the Reststrahlen response in hexagonal boron nitride across more than 5 orders of magnitude in thickness, down to a monolayer. We find that the high reflectivity plateau of the Reststrahlen band evolves into a single peak as the material enters the optically thin limit, within which two distinct regimes emerge: a strong-response regime dominated by coherent radiative decay and a weak-response regime dominated by damping. We show that this evolution can be explained by a simple two-dimensional sheet model that can be applied to a wide range of thin media.

Disparities in nonmelanoma skin cancer in Hispanic/Latino patients based on Mohs micrographic surgery defect size: A multicenter retrospective study.

BACKGROUND: There is limited literature regarding potential disparities in nonmelanoma skin cancer for patients with skin of color. OBJECTIVE: Use the sizes of Mohs micrographic surgery defects to examine disparities in nonmelanoma skin cancer among Hispanic/Latino patients with a secondary aim to examine the effect of insurance type. METHODS: We conducted a multicenter retrospective study using data from 3 major institutions in Los Angeles County. A total of 3486 Mohs micrographic surgeries of basal cell, squamous cell, and basosquamous cell carcinomas were analyzed. RESULTS: Mohs micrographic surgery defect sizes were 17% larger among Hispanic/Latino patients compared with non-Hispanic White patients. More notably, when comparing defect sizes of squamous cell carcinomas to those of basal cell carcinomas, defects were 80% larger among Hispanic/Latino patients compared to non-Hispanic White patients who had 25% larger defect sizes. Compared to patients with Medicare, patients with health maintenance organization and Medicaid/health maintenance organization had 22% and 52% larger defect sizes, respectively, whereas patients with preferred provider organization, had 10% smaller defect sizes. LIMITATIONS: The data included were from a single county population. CONCLUSION: Disparities regarding nonmelanoma skin cancer exist between patients with skin of color and White patients. Patients and the medical community need to be cognizant that skin cancer can develop in patients regardless of their race and ethnicity.

Temperature and Solvent Effects on H2 Splitting and Hydricity: Ramifications on CO2 Hydrogenation by a Rhenium Pincer Catalyst.

The catalytic hydrogenation of carbon dioxide holds immense promise for applications in sustainable fuel synthesis and hydrogen storage. Mechanistic studies that connect thermodynamic parameters with the kinetics of catalysis can provide new understanding and guide predictive design of improved catalysts. Reported here are thermochemical and kinetic analyses of a new pincer-ligated rhenium complex (tBuPOCOP)Re(CO)2 (tBuPOCOP = 2,6-bis(di-tert-butylphosphinito)phenyl) that catalyzes CO2 hydrogenation to formate with faster rates at lower temperatures. Because the catalyst follows the prototypical "outer sphere" hydrogenation mechanism, comprehensive studies of temperature and solvent effects on the H2 splitting and hydride transfer steps are expected to be relevant to many other catalysts. Strikingly large entropy associated with cleavage of H2 results in a strong temperature dependence on the concentration of [(tBuPOCOP)Re(CO)2H]- present during catalysis, which is further impacted by changing the solvent from toluene to tetrahydrofuran to acetonitrile. New methods for determining the hydricity of metal hydrides and formate at temperatures other than 298 K are developed, providing insight into how temperature can influence the favorability of hydride transfer during catalysis. These thermochemical insights guided the selection of conditions for CO2 hydrogenation to formate with high activity (up to 364 h-1 at 1 atm or 3330 h-1 at 20 atm of 1:1 H2:CO2). In cases where hydride transfer is the highest individual kinetic barrier, entropic contributions to outer sphere H2 splitting lead to a unique temperature dependence: catalytic activity increases as temperature decreases in tetrahydrofuran (200-fold increase upon cooling from 50 to 0 °C) and toluene (4-fold increase upon cooling from 100 to 50 °C). Ramifications on catalyst structure-function relationships are discussed, including comparisons between "outer sphere" mechanisms and "metal-ligand cooperation" mechanisms.

Initial skin cancer screening for solid organ transplant recipients in the United States: Delphi method development of expert consensus guidelines.

Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancer-associated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplant patients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2 years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5 years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer.

Dysphotopsia: a multifaceted optic phenomenon.

PURPOSE OF REVIEW: To summarize the literature on dysphotopsia, focusing on strategies for management and prevention. RECENT FINDINGS: Clinical studies and ray-tracing diagrams have improved our understanding of the risk factors for positive and negative dysphotopsiae. Well known management and prevention strategies such as piggyback IOL, reverse optic capture, Nd:YAG capsulotomy, and IOL exchange are reviewed, as well as newer strategies such as the infertemporal approach to IOL implantation, 'in-the-bag nasal optic truncation' and new IOL design implantation, and new IOL design. SUMMARY: Positive and negative dysphotopsiae are known to occur in a number of patients after cataract surgery. Although studying dysphotopsiae has provided many challenges given its subjective patient experience and its multifactorial cause, these same challenges have generated new theories and ideas regarding dysphotopsiae. A better understanding of the available methods for treatment and prevention can improve management of dysphotopsiae and patient satisfaction.

Pharmacodynamic Comparison of Prasugrel Versus Ticagrelor in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: The OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 Study.

BACKGROUND: Patients with diabetes mellitus (DM) are at increased risk of atherothrombotic events, underscoring the importance of effective platelet inhibiting therapies. Prasugrel and ticagrelor reduce thrombotic complications to a greater extent than clopidogrel. Subgroup analyses of pivotal clinical trials testing prasugrel and ticagrelor versus clopidogrel showed DM patients to have benefits that were consistent with the overall trial populations, although the magnitude of the ischemic risk reduction appeared to be enhanced with prasugrel. Whether these findings may be attributed to differences in the pharmacodynamic profiles of these drugs in DM patients remains poorly explored and represented the aim of this study. METHODS: In this prospective, randomized, double-blind, double-dummy, crossover pharmacodynamic study, aspirin-treated DM patients (n=50) with coronary artery disease were randomly assigned to receive prasugrel (60 mg loading dose [LD]/10 mg maintenance dose once daily) or ticagrelor (180 mg LD/90 mg maintenance dose twice daily) for 1 week. Pharmacodynamic assessments were conducted using 4 different assays, including VerifyNow P2Y12, vasodilator-stimulated phosphoprotein, light transmittance aggregometry, and Multiplate, which allowed us to explore ADP- and non-ADP-induced (arachidonic acid-, collagen-, thrombin receptor-activating, peptide-induced) platelet signaling pathways. The acute (baseline, 30 minutes, and 2 hours post-LD) and maintenance (1 week) effects of therapy were assessed. The primary end point of the study was the comparison of P2Y12 reaction units determined by VerifyNow P2Y12 at 1 week between prasugrel and ticagrelor. RESULTS: ADP- and non-ADP-induced measures of platelet reactivity reduced significantly with both prasugrel and ticagrelor LD and maintenance dose. P2Y12 reaction units defined by VerifyNow were similar between prasugrel and ticagrelor at 30 minutes and 2 hours post-LD. At 1 week, P2Y12 reaction units were significantly lower with ticagrelor than with prasugrel (52 [32-72] versus 83 [63-103]; least-square means difference: -31; 95% confidence interval, -57 to -4; P=0.022; primary end point). Pharmacodynamic assessments measured by vasodilator-stimulated phosphoprotein, light transmittance aggregometry, and Multiplate were similar between prasugrel and ticagrelor at each time point, including at 1 week. Rates of high on-treatment platelet reactivity were similar between groups with all assays at all time points. CONCLUSIONS: In DM patients with coronary artery disease, ticagrelor exerts similar or greater inhibition of ADP-induced platelet reactivity in comparison with prasugrel in the acute and chronic phases of treatment, whereas the inhibition of measures of non-ADP-induced platelet reactivity was not significantly different between the 2 agents. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01852214.

Mammalian DNA2 helicase/nuclease cleaves G-quadruplex DNA and is required for telomere integrity.

Efficient and faithful replication of telomeric DNA is critical for maintaining genome integrity. The G-quadruplex (G4) structure arising in the repetitive TTAGGG sequence is thought to stall replication forks, impairing efficient telomere replication and leading to telomere instabilities. However, pathways modulating telomeric G4 are poorly understood, and it is unclear whether defects in these pathways contribute to genome instabilities in vivo. Here, we report that mammalian DNA2 helicase/nuclease recognizes and cleaves telomeric G4 in vitro. Consistent with DNA2's role in removing G4, DNA2 deficiency in mouse cells leads to telomere replication defects, elevating the levels of fragile telomeres (FTs) and sister telomere associations (STAs). Such telomere defects are enhanced by stabilizers of G4. Moreover, DNA2 deficiency induces telomere DNA damage and chromosome segregation errors, resulting in tetraploidy and aneuploidy. Consequently, DNA2-deficient mice develop aneuploidy-associated cancers containing dysfunctional telomeres. Collectively, our genetic, cytological, and biochemical results suggest that mammalian DNA2 reduces replication stress at telomeres, thereby preserving genome stability and suppressing cancer development, and that this may involve, at least in part, nucleolytic processing of telomeric G4.

Voriconazole increases the risk for cutaneous squamous cell carcinoma after lung transplantation.

Lung transplant recipients (LTR) are at high risk of cutaneous squamous cell carcinoma (SCC). Voriconazole exposure after lung transplant has recently been reported as a risk factor for SCC. We sought to study the relationship between fungal prophylaxis with voriconazole and the risk of SCC in sequential cohorts from a single center. We evaluated 400 adult LTR at UCLA between 7/1/2005 and 12/22/2012. On 7/1/2009, our center instituted a protocol switch from targeted to universal antifungal prophylaxis for at least 6 months post-transplant. Using Cox proportional hazards models, time to SCC was compared between targeted (N = 199) and universal (N = 201) prophylaxis cohorts. Cox models were also used to assess SCC risk as a function of time-dependent cumulative exposure to voriconazole and other antifungal agents. The risk of SCC was greater in the universal prophylaxis cohort (HR 2.02, P < 0.01). Voriconazole exposure was greater in the universal prophylaxis cohort, and the cumulative exposure to voriconazole was associated with SCC (HR 1.75, P < 0.01), even after adjustment for other important SCC risk factors. Voriconazole did not increase the risk of advanced tumors. Exposure to other antifungal agents was not associated with SCC. Voriconazole should be used cautiously in this population.