Controlling the Balance between Remote, Pinhole, and van der Waals Epitaxy of Heusler Films on Graphene/Sapphire.

Remote epitaxy is promising for the synthesis of lattice-mismatched materials, exfoliation of membranes, and reuse of expensive substrates. However, clear experimental evidence of a remote mechanism remains elusive. Alternative mechanisms such as pinhole-seeded epitaxy or van der Waals epitaxy can often explain the resulting films. Here, we show that growth of the Heusler compound GdPtSb on clean graphene/sapphire produces a 30° rotated (R30) superstructure that cannot be explained by pinhole epitaxy. With decreasing temperature, the fraction of this R30 domain increases, compared to the direct epitaxial R0 domain, which can be explained by a competition between remote versus pinhole epitaxy. Careful graphene/substrate annealing and consideration of the relative lattice mismatches are required to obtain epitaxy to the underlying substrate across a series of other Heusler films, including LaPtSb and GdAuGe. The R30 superstructure provides a possible experimental fingerprint of remote epitaxy, since it is inconsistent with the leading alternative mechanisms.

Improved erythema and decreased blister formation in dominant dystrophic epidermolysis bullosa following treatment with pulsed dye laser.

Dominant dystrophic epidermolysis bullosa (DDEB), an inherited disorder due to type VII collagen mutations, is characterized by blisters and erosions that heal with scarring, atrophy, and milia. There is no established role for laser in the management of patients with DDEB. Pulsed dye laser (PDL) is most often used to target vascular skin lesions. We describe a patient with DDEB with marked improvement in erythema as well as fewer and less symptomatic episodes of blistering following treatment with PDL.

Perioperative Serum 25-Hydroxyvitamin D Levels as a Predictor of Postoperative Opioid Use and Opioid Use Disorder: a Cohort Study.

IMPORTANCE: Vitamin D deficiency is associated with chronic pain syndromes and higher opioid use among cancer patients, but its association with opioid use among opioid-naïve subjects following a major surgical procedure with acute pain has not been explored. OBJECTIVE: To determine the association between serum 25-hydroxyvitamin D (25(OH)D) levels, opioid use, and opioid use disorder. METHODS: We identified commercially insured subjects aged 18-64 years with available perioperative serum 25-hydroxyvitamin D (25D) levels who underwent one of nine major surgical procedures in 2000-2014. Primary outcomes were dose and duration of opioid use measured using pharmacy claims. Secondary outcome was opioid use disorder captured using diagnosis codes. Multivariable negative binomial models with generalized estimating equations were performed examining the association between 25D levels and postoperative opioid use measures, adjusting for age, sex, race/ethnicity, Charlson score, education, income, latitude, and season of blood draw. Adjusted Cox regression was used to examine the association with opioid use disorder. RESULTS: Among 5446 subjects, serum 25(OH)D was sufficient (≥ 20 ng/mL) among 4349 (79.9%) subjects, whereas 837 (15.4%) had insufficient (12 to < 20 ng/mL) and 260 (4.8%) had deficient (< 12 ng/mL) levels. On multivariable analysis, as compared with subjects with sufficient 25(OH)D levels, subjects with deficient 25(OH)D levels had 1.7 more days (95% CI 0.76, 2.58) of opioid use per year and had 98.7 higher morphine milligram equivalent dose (95% CI 55.7, 141.8) per year. Among 11,713 study cohort, subjects with deficient 25(OH)D levels were more likely to be diagnosed with opioid use disorders (HR 2.41; 95% CI 1.05, 5.52). CONCLUSION: Patients undergoing common surgical procedures with deficient 25D levels are more likely to have higher opioid use and an increased risk of opioid use disorder compared to those with sufficient levels. Serum 25D levels may serve as a biomarker to identify subjects at increased risk of opioid misuse.

A pediatric approach to management of skin growths in basal cell nevus syndrome.

Little guidance on management of basal cell nevus syndrome in children exists. We report a case series of four patients diagnosed with BCNS in early childhood, in whom several highly suspicious lesions were biopsied, but several smaller and questionably concerning lesions were treated with therapies that are more tolerable for children, including topical imiquimod, 5-fluorouracil, cryotherapy, or touch electrodessication following topical anesthetic cream. These therapies were well tolerated, and all residual or persistent lesions were subsequently biopsied and found to be benign. This approach is often preferable for pediatric BCNS patients, in whom concerning lesions can be identified clinically and managed compassionately. However, any lesion that exhibits growth, bleeding, or symptoms should be biopsied for definitive diagnosis.

Comparative effectiveness of treatment of actinic keratosis with topical fluorouracil and imiquimod in the prevention of keratinocyte carcinoma: A cohort study.

BACKGROUND: The effectiveness of 5-fluorouracil compared with that of imiquimod for preventing keratinocyte carcinoma is unknown. OBJECTIVE: To compare the effectiveness of 5-fluorouracil and that of imiquimod in preventing keratinocyte carcinoma in a real-world practice setting. METHODS: We identified 5700 subjects who filled prescriptions for 5-fluorouracil or imiquimod for treatment of actinic keratosis in 2007. An intention-to-treat analysis controlling for potential confounding variables was used to calculate 2- and 5-year cumulative risk differences for subsequent keratinocyte carcinoma overall and in field-treated areas. RESULTS: 5-Fluorouracil was associated with a statistically significant decreased risk of any keratinocyte carcinoma compared with imiquimod (adjusted hazard ratio [aHR], 0.86; 95% confidence interval [CI], 0.76-0.97), but there were no significant differences in risk by tumor subtype (for squamous cell carcinoma: aHR, 0.89; 95% CI, 0.74-1.07; for basal cell carcinoma: aHR, 0.87; 95% CI, 0.74-1.03) or site-specific keratinocyte carcinoma (aHR, 0.96; 95% CI, 0.81-1.14). There were no significant differences in 2- or 5-year cumulative risk of keratinocyte carcinoma among those treated with 5-fluorouracil versus with imiquimod. LIMITATIONS: Generalizability to other practice settings may be limited. CONCLUSIONS: Whereas 5-fluorouracil was more effective in reducing keratinocyte carcinoma risk overall, we found no differences in the short- or long-term risk of subsequent site-specific keratinocyte carcinoma in a real-world practice setting.

Nucleation Selectivity and Lateral Coalescence of GaAs over Graphene on Ge(111).

We use epitaxial lateral overgrowth (ELO) to produce semimetallic graphene nanostructures embedded in a semiconducting GaAs matrix for potential applications in plasmonics, THz generation and detection, and tunnel junctions in multijunction solar cells. We show that (1) the combination of low sticking coefficient and fast surface diffusion on graphene enhances nucleation selectivity at exposed regions of the substrate and (2) high growth temperatures favor efficient lateral overgrowth, coalescence, and planarization of epitaxial GaAs films over the graphene nanostructures. Our work provides a more complete understanding of ELO using graphene masks, as opposed to more conventional dielectric masks, and enables new types of metal/semiconductor nanocomposites.

Quantifying Mn Diffusion through Transferred versus Directly Grown Graphene Barriers.

We quantify the mechanisms for manganese (Mn) diffusion through graphene in Mn/graphene/Ge (001) and Mn/graphene/GaAs (001) heterostructures for samples prepared by graphene layer transfer versus graphene growth directly on the semiconductor substrate. These heterostructures are important for applications in spintronics; however, challenges in synthesizing graphene directly on technologically important substrates such as GaAs necessitate layer transfer and annealing steps, which introduce defects into the graphene. In situ photoemission spectroscopy measurements reveal that Mn diffusion through graphene grown directly on a Ge (001) substrate is 1000 times lower than Mn diffusion into samples without graphene (Dgr,direct ∼ 4 × 10-18 cm2/s, Dno-gr ∼ 5 × 10-15 cm2/s at 500 °C). Transferred graphene on Ge suppresses the Mn in Ge diffusion by a factor of 10 compared to no graphene (Dgr,transfer ∼ 4 × 10-16 cm2/s). For both transferred and directly grown graphene, the low activation energy (Ea ∼ 0.1-0.5 eV) suggests that Mn diffusion through graphene occurs primarily at graphene defects. This is further confirmed as the diffusivity prefactor, D0, scales with the defect density of the graphene sheet. Similar diffusion barrier performance is found on GaAs substrates; however, it is not currently possible to grow graphene directly on GaAs. Our results highlight the importance of developing graphene growth directly on functional substrates to avoid the damage induced by layer transfer and annealing.

Sex-based differences in the anatomic distribution of cutaneous squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in the United States, and its incidence is increasing. Ultraviolet radiation is the main environmental risk factor for cSCCs; thus, they tend to arise on sun-exposed skin. Most publications cite the head and neck as the predominant location for cSCCs, but these papers do not account for the differential anatomic predication of cSCCs by sex. No prior studies have examined the differential distribution of cSCCs by sex, particularly invasive cSCCs that have the potential for recurrence and metastasis. OBJECTIVE: We examined the association between cSCC tumor features, including anatomic site and invasiveness, by key patient features, including age and sex. METHODS: Using an institutional cSCC registry, we identified 618 non-Hispanic white patients diagnosed with 2,111 histologically-confirmed cSCCs between 2000-2016. RESULTS: We found differential anatomic distributions of cSCC by patient sex. Men were more likely to have cSCCs arise on the head and neck (51.7%), whereas women were more likely to have cSCCs develop on the lower extremity (41.2%). Stratification by dichotomized age (younger [<65 years] vs. older [≥65 years]) revealed that nearly half of invasive cSCCs (47.7%) among older women arose on the lower extremities, whereas approximately half of the invasive cSCCs (52.4%) arose on the head and neck among older men. CONCLUSION: Lower extremities can be easily overlooked, particularly when practitioners perform waist-up-only skin examinations in time-limited settings. Understanding the anatomic predilection for invasive cSCCs by patient characteristics, including our findings, which suggest that the lower extremities are an important anatomic site for invasive cSCCs among women, can help further inform skin cancer screening and prevention efforts.

Spiking neurons from tunable Gaussian heterojunction transistors.

Spiking neural networks exploit spatiotemporal processing, spiking sparsity, and high interneuron bandwidth to maximize the energy efficiency of neuromorphic computing. While conventional silicon-based technology can be used in this context, the resulting neuron-synapse circuits require multiple transistors and complicated layouts that limit integration density. Here, we demonstrate unprecedented electrostatic control of dual-gated Gaussian heterojunction transistors for simplified spiking neuron implementation. These devices employ wafer-scale mixed-dimensional van der Waals heterojunctions consisting of chemical vapor deposited monolayer molybdenum disulfide and solution-processed semiconducting single-walled carbon nanotubes to emulate the spike-generating ion channels in biological neurons. Circuits based on these dual-gated Gaussian devices enable a variety of biological spiking responses including phasic spiking, delayed spiking, and tonic bursting. In addition to neuromorphic computing, the tunable Gaussian response has significant implications for a range of other applications including telecommunications, computer vision, and natural language processing.

Short peptide sequences mimic HLA-DM functions.

HLA-DM (DM) plays a critical role in Ag presentation to CD4 T cells by catalyzing the exchange of peptides bound to MHC class II molecules. It is known that DM interaction with MHC II involves conformational changes in the MHC II molecule leading to the disturbance of H-bonds formed between the bound peptide and the MHC II groove leading to peptide dissociation. The specific region of the DM molecule that induces this peptide dissociation is not defined. In this study, we describe three short peptides (helper peptides) that accelerate DM-catalyzed peptide exchange. Kinetic studies presented here demonstrate that these peptides act similarly to DM in; (a) enhancing peptide binding to HLA-DR1; (b) dissociation of complexes of peptide-DR1; and (c) maintaining a receptive conformation of empty DR1. We further report that helper peptides are effective in increasing peptide binding to DR1 expressed on B cells in vitro, and, when mixed with peptide and adjuvant, cause enhanced T cell priming in HLA-DR1 Tg mice. We suggest that helper peptides might interact with the same critical residues on MHC class II that is targeted by DM.

Case Volume-to-Outcome Relationship in Minimally Invasive Esophagogastrectomy.

BACKGROUND: Outcomes after open esophagogastrectomy (OE) have been shown to depend on institution case volume. We aim to determine whether a similar relationship exists for minimally invasive esophagogastrectomy (MIE). METHODS: Patients who had OE or MIE (excluding robotic procedures) between 2010 and 2013 in the National Cancer Database were included. Outcomes included 30-day and 90-day mortality, length of stay, hospital readmission, margin positivity, and number of lymph nodes harvested. Logistic and linear regression were used to adjust for possible confounders including age, sex, tumor size, Charlson score, induction therapy, and type of institution (academic versus community based). RESULTS: We identified 2371 patients in the MIE group and 6285 patients in the OE group. In multivariate analysis, high case volume was an independent predictor for lower 30-day mortality and 90-day mortality, shorter length of stay, and higher rate of negative-margin resection in OE (P < .001) but not in MIE. After quartile ranking of institutions based on volume, MIE outcomes were found to be better in institutions in the highest volume quartile compared with those in the lowest (P < .001). CONCLUSIONS: In this dataset, MIE postoperative outcomes, unlike OE postoperative outcomes, did not correlate with hospital case volume. Volume-outcome relationships may be affected by surgical approach. The effect of case volume on long-term outcomes after MIE warrants further study.

Characteristics of cardiothoracic surgeons practicing at the top-ranked US institutions.

BACKGROUND: We aimed to determine which factors distinguish cardiothoracic (CT) surgeons practicing at the top-ranked US institutions from their peers. METHODS: Using online resources, we collected demographics, training information and academic metrics of 694 cardiac (n=489; 70%) and thoracic (n=205; 30%) surgeons practicing at 57 preeminent US institutions, including those with the highest US News & World Report ranking ("top CT centers"). RESULTS: Two hundred and ninety-nine (43.1%) CT surgeons were practicing at the 18 "top CT centers" and had higher academic productivity (publications, citations) than their peers. While there was no difference in the proportion of international medical graduates (IMGs) (21.4% overall) or of surgeons with a PhD degree (9.4% overall) across institutions, the "top CT centers" had a higher proportion of faculty who received their entire CT training abroad (10.4% vs. 5.8%; P=0.038) or at highly-ranked US institutions. Those who published more during their early career years (residency, fellowship and first 5 years as faculty) were more likely to attain academic (professorship) and institutional leadership (division/department chair) positions and to practice at the "top CT centers". Women represented a minority (7.3% overall; 5.1% of cardiac vs. 12.7% of thoracic surgeons, P<0.001), but with growing prevalence among younger faculty and without differences across institutions. CONCLUSIONS: CT surgeons of the best US centers have a more international background and received their training at highly-ranked institutions. Early academic productivity is associated with life-long career achievements, with special importance of the first 5 years as faculty. Women represent a growing proportion of the CT surgical workforce.

HLA-DM mediates peptide exchange by interacting transiently and repeatedly with HLA-DR1.

The peptide editor HLA-DM (DM) catalyzes the exchange of peptides bound to MHC class II molecules within antigen presenting cells by generating a "peptide-receptive" MHC class II conformation (MHC(receptive)) to which peptides readily bind and rapidly unbind. While recent work has uncovered the determinants of DM recognition and effector functions, the nature of MHC(receptive) and its interaction with DM remains unclear. Here, we show that DM induces but does not stabilize MHC(receptive) in the absence of peptides. We demonstrate that DM is out-competed by certain superantigens, and increasing solvent viscosity inhibits DM-induced peptide association. We suggest that DM mediates peptide exchange by interacting transiently and repeatedly with MHC class II molecules, continually generating MHC(receptive). The simultaneous presence of peptide and DM in the milieu is thus crucial for the efficient generation of specific peptide-MHC class II complexes over time.