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BACKGROUND AND OBJECTIVE: To provide an overview of progressive retinoschisis-related retinal detachment (RSRD) management at a tertiary referral center. MATERIALS AND METHODS: Single-institution retrospective case series from January 1, 2003, to May 1, 2020. RESULTS: Progressive RSRD occurred in 0.9% of patients with retinoschisis. Mean (range) age at time of surgery was 58.7 years (40.0 to 74.0). Ten eyes were initially treated with scleral buckle, three eyes with vitrectomy, and three eyes with combined scleral buckle and vitrectomy. Overall reattachment rate was 100.0%; single-surgery success was 56.2%. Proliferative vitreoretinopathy developed in 10.0% of scleral buckles, 33.3% of vitrectomies, and 33.3% of combined surgeries. CONCLUSIONS: Progressive RSRD is rare and poses surgical management challenges. Final retinal attachment can be achieved successfully but often requires secondary and staged surgeries. Localization of outer retinal breaks may help guide surgical management. Further research—such as a large-scale, prospective, multicenter, randomized trial—would be needed to determine the optimal surgical technique. [ Ophthalmic Surg Lasers Imaging Retina . 2022;53:132–138.]

To report an atypical presentation of postoperative endophthalmitis after cataract surgery that initially presented as angle-closure glaucoma and to discuss challenges with the case management due to the unusual presentation and patient non-compliance.Observational case report. B-scan ultrasound and ultrasound biomicroscopy.A 69-year-old Caucasian male with a 1-week history of uncomplicated cataract surgery was referred to our glaucoma clinic due to vision loss and concern for angle closure glaucoma. Anterior segment exam showed 360 degrees of flat anterior chamber (AC) with no hypopyon. A diagnosis of postoperative endophthalmitis was established when a B-scan ultrasound showed dense vitreous opacities. The patient underwent a pars plana vitrectomy (PPV), AC reformation, peripheral iridectomy, and intravitreal injection of antibiotics for treatment of endophthalmitis in the presence of an angle-closure glaucoma with good visual recovery.A low threshold for suspicion of endophthalmitis is needed after any routine intraocular procedure. An atypical presentation may masquerade as another pathology that delays the true diagnosis and treatment. Timely intervention in postoperative endophthalmitis is crucial in preserving vision.

BackgroundCurrent melphalan-based intravitreal regimens for retinoblastoma (RB) vitreous seeds cause retinal toxicity. We assessed the efficacy and toxicity of topotecan monotherapy compared with melphalan in our rabbit model and patient cohort.MethodsRabbit experiments: empiric pharmacokinetics were determined following topotecan injection. For topotecan (15 μg or 30 µg), melphalan (12.5 µg) or saline, toxicity was evaluated by serial electroretinography (ERG) and histopathology, and efficacy against vitreous seed xenografts was measured by tumour cell reduction and apoptosis induction. Patients: retrospective cohort study of 235 patients receiving 990 intravitreal injections of topotecan or melphalan.ResultsIntravitreal topotecan 30 µg (equals 60 µg in humans) achieved the IC90 across the rabbit vitreous. Three weekly topotecan injections (either 15 µg or 30 µg) caused no retinal toxicity in rabbits, whereas melphalan 12.5 µg (equals 25 µg in humans) reduced ERG amplitudes 42%–79%. Intravitreal topotecan 15 µg was equally effective to melphalan to treat WERI-Rb1 cell xenografts in rabbits (96% reduction for topotecan vs saline (p=0.004), 88% reduction for melphalan vs saline (p=0.004), topotecan vs melphalan, p=0.15). In our clinical study, patients received 881 monotherapy injections (48 topotecan, 833 melphalan). Patients receiving 20 µg or 30 µg topotecan demonstrated no significant ERG reductions; melphalan caused ERG reductions of 7.6 μV for every injection of 25 µg (p=0.03) or 30 µg (pConclusionsTaken together, these experiments suggest that intravitreal topotecan monotherapy for the treatment of RB vitreous seeds is non-toxic and effective.

Purpose To compare retinal toxicity as measured by electroretinogram, ocular, and patient survival in retinoblastoma treated with intravitreal melphalan at two concentrations (25 vs. 30 µg). Methods Single-center, retrospective analysis of retinoblastoma eyes receiving 25-µg or 30-µg intravitreal melphalan from September 2012 to January 2019. Ocular toxicity was measured by electroretinogram of evaluable injections in 449 injections in 136 eyes. A repeated-measures linear mixed model with a random intercept and slope was applied to account for repeated measures for each eye. Results Average decline in electroretinogram after each additional injection was -4.9 µV (95% confidence interval -6.3 to -3.4); electroretinogram declined by -4.6 µV (95% confidence interval -7.0 to -2.2) after 25-µg injections and -5.2 µV (95% confidence interval -6.6 to -3.8) after 30-µg injections (P = 0.66). Injection at a new clock site hour was associated with a -3.91-µV lower average (95% confidence interval -7.8 to -0.04). Conclusion Electroretinogram-measured toxicity in retinoblastoma eyes treated with intravitreal injections was not found to be different across 25-µg and 30-µg injections. There were no cases of extraocular extension or metastatic deaths in our patient population.

Background Primary vitreoretinal lymphoma (PVRL) is an aggressive lymphoma that may present with protean features and represents a diagnostic challenge. Given that patients with PVRL are at high risk of CNS involvement with a high mortality and morbidity rate, prompt diagnosis is crucial to initiate treatment early in the disease course. A multimodality imaging approach including fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), fluorescein and indocyanine angiography, and electroretinography (ERG) can provide information to establish a diagnosis and provide objective measures for management. We review key findings seen via these imaging modalities in patients with PVRL. Observations Fundus photography can highlight commonly seen patterns of PVRL including vitritis, subretinal disease, retinal pigment epithelial (RPE) abnormalities, optic nerve edema, retinal detachment, and less typical retinitis-like lesions. FAF can identify characteristic patterns of hyper- and hypoautofluorescent signal abnormalities in the macula. Spectral-domain OCT will demonstrate vitreous cells, RPE nodularity, and hyperreflectivity of the outer retina. The presence of a hyper-reflective band in the subretinal space and infiltrates between the RPE and Bruch’s membrane can assist in distinguishing PVRL from choroidal lymphoma. Vertical hyperreflective columns (VHRLs) are another pertinent finding that may represent microinfiltrates of the tumor. OCT has proven to be a particularly useful modality in assessing the progress of treatment in PVRL. Fluorescein angiography can show RPE changes, which include granularity, late staining at the RPE level, and blockage. Indocyanine green angiography (ICGA) primarily shows hypocyanescence, which corresponds to PVRL lesions on fundus photography and may occur secondary to loss of RPE and choriocapillaris. Conclusion While PVRL remains a challenging disease to diagnose and follow, the use of a multimodality imaging approach may assist in establishing a diagnosis. Because of the anatomic spaces PVRL may affect, fundus photography, OCT, FAF, angiography, and ERG can identify key characteristics of the disease, differentiate PVRL from other diseases, and provide baseline information for targeted systemic and local therapies. Further assessment of anatomic and functional targets will aid our clinical application of multimodal imaging in the management of PVRL.

Purpose Explore the spectrum of clinical manifestations of pentosan polysulfate sodium (PPS) maculopathy observed across a range of practice settings. Design Multi-institutional retrospective study. Participants Patients exhibiting findings suggestive of PPS maculopathy identified from April 30, 2019, to December 4, 2020. Methods Members of the Macula Society submitted cases of presumed PPS maculopathy for consideration in this series. Diagnosis was confirmed by masked review of fundus imaging. Clinical characteristics of confirmed cases were summarized with descriptive statistics. Main Outcome Measures Pentosan polysulfate exposure characteristics and fundus imaging features. Results There were 74 patients with PPS maculopathy included in the current study. Median (interquartile range) age at diagnosis was 62.0 years (56.0–65.8). The median duration of exposure to PPS was 14.0 years (10.2–18.9), with a median cumulative exposure of 1.5 kg (0.9–2.4). The most common presenting symptom was decreased or blurry vision (66.2%), followed by prolonged dark adaption or nyctalopia (32.4%). The most common referral diagnosis was age-related macular degeneration (54.1%); 16.2% of patients were referred for suspected PPS maculopathy. Novel imaging findings emerged, including highly asymmetric disease in 2 patients and a prominent vitelliform maculopathy in 2 patients. Conclusions Most patients with PPS maculopathy exhibit characteristic findings on multimodal fundus imaging in the setting of high cumulative exposure to the oral drug. Some patients in the current study manifested novel imaging findings, expanding our understanding of the phenotypic spectrum of this condition. We recommend considering standardized ophthalmic screening of patients treated with PPS.

The use of intravitreal chemotherapy has revolutionized the treatment of advanced intraocular retinoblastoma, as intravitreal melphalan has enabled difficult-to-treat vitreous tumor seeds to be controlled, leading to many more eyes being saved. However, melphalan hydrochloride (MH) degrades rapidly in solution, increasing logistical complexity with respect to time between medication preparation and administration for intravitreal administration under anesthesia for retinoblastoma. A new propylene glycol-free melphalan (PGFM) formulation has greater stability and could therefore improve access and adoption of intravitreal chemotherapy, allowing more children to retain their eye(s). We compared the efficacy and toxicity of both formulations, using our rabbit xenograft model and clinical patient experience. Three weekly 12.5μg intravitreal injections of MH or PGFM (right eye), and saline (left eye), were administered to immunosuppressed rabbits harboring human WERI-Rb1 vitreous seed xenografts. Residual live cells were quantified directly, and viability determined by TUNEL staining. Vitreous seeds were reduced 91% by PGFM (p=0.009), and 88% by MH (p=0.004; PGFM vs. MH: p=0.68). All residual cells were TUNEL-positive (non-viable). In separate experiments to assess toxicity, three weekly 12.5μg injections of MH, PGFM, or saline were administered to non-tumor-bearing rabbits. Serial electroretinography, optical coherence tomography (OCT) and OCT-angiography were performed. PGFM and MH both caused equivalent reductions in electroretinography amplitudes, and loss of retinal microvasculature on OCT-angiography. The pattern of retinal degeneration observed on histopathology suggested that segmental retinal toxicity associated with all melphalan formulations was due to a vitreous concentration gradient-effect. Efficacy and toxicity were assessed for PGFM given immediately (within 1 hour of reconstitution) vs. four hours after reconstitution. Immediate- and delayed-administration of PGFM showed equivalent efficacy and toxicity. In addition, we evaluated efficacy and toxicity in patients (205 eyes) with retinoblastoma vitreous seeds, which were treated with a total of 833 intravitreal injections of either MH or PGFM as standard of care. Of these, we analyzed 118 MH and 131 PGFM monotherapy injections in whom serial ERG measurements were available to model retinal toxicity. Both MH and PGFM caused reductions in electroretinography amplitudes, but with no statistical difference between formulations. Comparing those patient eyes treated exclusively with PGFM versus those treated exclusively with MH, efficacy for tumor control and globe salvage was equivalent (PGFM vs. MH: 96.2% vs. 93.8%, p=0.56), but PGFM-treated eyes received fewer injections than MH-treated eyes (average 3.2±1.9 vs. 6.4±2.1 injections, p

Background Exposure to the plastic surgery department is an important experience for medical students interested in the field. However, the impact of medical students in the plastic surgery operating room has not been previously examined. The aim of this study is to understand whether the presence of medical students impacted overall procedure time and postoperative complications for bilateral reduction mammoplasties. Materials and methods A retrospective review was performed on all patients who underwent bilateral reduction mammoplasty from January 2010 to December 2015. Procedures were divided into operations with medical students present and operations without medical students present. Patient average operation time and average procedure time were analyzed. A 2-tailed t-test was used to compare times with statistical significance set at P less than 0.05. A multivariate regression analysis was performed to control for potential confounders. Results A total of 157 patients underwent bilateral reduction mammoplasties. Seventy-five of these cases had at least 1 medical student present; 82 of these cases had no medical student present. Patient information was not statistically different between groups. The average total operative time was 150.32 minutes, and the average procedure time (skin-incision to skin-closure) was 109.15 minutes. The total operative time was significantly longer in procedures with medical students: 158.25 minutes versus 143.06 minutes in procedures without medical students (P = 0.013). However, the total procedure time was not significantly longer: 113.95 minutes with medical students versus 104.75 minutes without medical students (P = 0.096). There were no differences in perioperative complications and multivariate regression analysis showed no statistically significant confounders for the duration of surgery.

The broadband photothermoelectric effect has been studied on a graphene-2D semiconductor lateral heterojunction., The massless Dirac electron transport in graphene has led to a variety of unique light-matter interaction phenomena, which promise many novel optoelectronic applications. Most of the effects are only accessible by breaking the spatial symmetry, through introducing edges, p-n junctions, or heterogeneous interfaces. The recent development of direct synthesis of lateral heterostructures offers new opportunities to achieve the desired asymmetry. As a proof of concept, we study the photothermoelectric effect in an asymmetric lateral heterojunction between the Dirac semimetallic monolayer graphene and the parabolic semiconducting monolayer MoS2. Very different hot-carrier cooling mechanisms on the graphene and the MoS2 sides allow us to resolve the asymmetric thermalization pathways of photoinduced hot carriers spatially with electrostatic gate tunability. We also demonstrate the potential of graphene-2D semiconductor lateral heterojunctions as broadband infrared photodetectors. The proposed structure shows an extreme in-plane asymmetry and provides a new platform to study light-matter interactions in low-dimensional systems.

The controlled synthesis of large-area, atomically thin molybdenum ditelluride (MoTe2) crystals is crucial for its various applications based on the attractive properties of this emerging material. In this work, we developed a chemical vapor deposition synthesis to produce large-area, uniform, and highly crystalline few-layer 2H and 1T' MoTe2 films. It was found that these two different phases of MoTe2 can be grown depending on the choice of Mo precursor. Because of the highly crystalline structure, the as-grown few-layer 2H MoTe2 films display electronic properties that are comparable to those of mechanically exfoliated MoTe2 flakes. Our growth method paves the way for the large-scale application of MoTe2 in high-performance nanoelectronics and optoelectronics.

Purpose To refine the Minnesota Grading System (MGS) using definitions from the Age-Related Eye Disease Studies (AREDS) into a nine-step grading scale (MGS-9). Methods A nine-step grading scale descriptive analysis using three key phenotypic features (total drusen area, increased, and decreased pigmentation) of human eyebank eyes that were graded according to definitions from the AREDS criteria in order to harmonize studies of disease progression for research involving human tissue. From 2005 through February 2017, we have analyzed 1159 human eyes, procured from two eyebanks. Each macula was imaged using high-resolution, stereoscopic color fundus photography with both direct- and transillumination. Fundus images were digitally overlaid with a grading template and triangulated for foveal centration. Results We documented and stratified risk for each globe by applying the AREDS nine-step grading scale to the key clinical features from the MGS-9. We found a good distribution within the MGS categories (1-9) with few level eight globes. Eyes were processed within 12.1 ± 6.3, hours from the time of death through imaging, dissection, and freezing or fixation. Applying the MGS-9 to 331 pairs (662 eyes were simultaneously graded), 84% were within one-grading step and 93% within two steps of the fellow eye. We also document reticular pseudodrusen, basal laminar drusen, and pattern dystrophy. Conclusions The MGS nine-step grading scale enables researchers using human tissue to refine the risk assessment of donor tissue. This analysis will harmonize results among researchers when grading human tissue using MGS criteria. Most importantly, the MGS-9 links directly to the known risk for progression from the AREDS.

Purpose The purpose of this study was to correlate magnetic resonance imaging (MRI) radiographic results with histopathologic growth patterns of metastatic uveal melanoma (UM) to the liver. Design Clinicopathologic correlation. Participants Patients with metastatic UM to the liver. Methods A retrospective review of MRI images of patients with metastatic UM to the liver at a single institution between 2004 and 2016 was performed. The MRI growth patterns were classified as nodular or diffuse. The histopathologic findings of core liver biopsies of liver metastases identified by needle localization in a subset of these patients were reviewed. The core samples were evaluated by routine light microscopy, including immunohistochemical/immunofluorescent staining for CD31, CD105, and HMB45, and classified as exhibiting an infiltrative or nodular growth pattern. Main Outcome Measures Magnetic resonance images and core biopsy findings. Results A total of 32 patients were identified with metastatic UM to the liver that was imaged by MRI, and 127 lesions were identified. A total of 46 lesions were classified by MRI as infiltrative and 81 as nodular. There were 9 needle-localized core biopsies that corresponded to MRI of metastatic lesions. Of these 9 lesions, 3 that were classified as infiltrative on MRI exhibited stage I infiltrative histologic growth patterns; of the remaining 6 that were classified as nodular by MRI, 5 histologically demonstrated stage II or stage III infiltrative growth patterns and 1 histologically demonstrated a nodular growth pattern. Conclusions Magnetic resonance imaging of hepatic infiltrative growth patterns of metastatic UM corresponded to stage I histologic infiltrative growth in the sinusoidal spaces, whereas MRI nodular growth patterns corresponded to stage II/III histologic infiltrative growth that replaced the hepatic lobule or histologic nodular growth in the portal triad that effaced adjacent hepatic parenchyma.

There has been an increasing demand for reconstructive surgery in acute or chronic groin wounds resulting from burn, trauma patients with oncologic defects following groin lymphadenectomy due to urogenital and lower limb malignancies and complications of infrainguinal vascular bypass surgeries. The reconstructive surgeon has to select the optimal soft tissue coverage after considering the patient’s comorbidities, postoperative quality of life, and functional outcome. In this chapter, we will review the reconstructive options regarding complex wounds in the inguinal region, a brief description of the reconstructive technique, reported outcomes, and comparison between options including use of grafts and flaps.

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy with a high propensity for regional lymph node metastasis and recurrence. Acute febrile neutrophilic dermatosis (Sweet syndrome) is an acute inflammatory skin eruption that is commonly associated with hematologic malignancies, but cases in association with solid tumors have also been reported. We present the first case of a 49-year-old female who experienced an acute flare up of Sweet syndrome during her initial diagnosis and subsequent treatment for MCC.

Proteasome inhibition is an approved cancer therapy. Quiescent fibroblasts are much more resistant to proteasome inhibition–induced death than proliferating fibroblasts. Mechanisms that protect quiescent fibroblasts include autophagy/lysosomal pathways, diminished aggresome formation, and detoxification of reactive oxygen species., Proteasome inhibition is used as a treatment strategy for multiple types of cancers. Although proteasome inhibition can induce apoptotic cell death in actively proliferating cells, it is less effective in quiescent cells. In this study, we used primary human fibroblasts as a model system to explore the link between the proliferative state of a cell and proteasome inhibition–mediated cell death. We found that proliferating and quiescent fibroblasts have strikingly different responses to MG132, a proteasome inhibitor; proliferating cells rapidly apoptosed, whereas quiescent cells maintained viability. Moreover, MG132 treatment of proliferating fibroblasts led to increased superoxide anion levels, juxtanuclear accumulation of ubiquitin- and p62/SQSTM1-positive protein aggregates, and apoptotic cell death, whereas MG132-treated quiescent cells displayed fewer juxtanuclear protein aggregates, less apoptosis, and higher levels of mitochondrial superoxide dismutase. In both cell states, reducing reactive oxygen species with N-acetylcysteine lessened protein aggregation and decreased apoptosis, suggesting that protein aggregation promotes apoptosis. In contrast, increasing cellular superoxide levels with 2-methoxyestradiol treatment or inhibition of autophagy/lysosomal pathways with bafilomycin A1 sensitized serum-starved quiescent cells to MG132-induced apoptosis. Thus, antioxidant defenses and the autophagy/lysosomal pathway protect serum-starved quiescent fibroblasts from proteasome inhibition–induced cytotoxicity.

The inhibitors of apoptosis (IAP) are important regulators of apoptosis. However, little is known about the capacity of Smac mimetics (IAP inhibitor) to overcome virally associated-lymphoma's (VAL) resistance to apoptosis. Here, we explored the pro-apoptotic effect of a novel Smac mimetic, RMT5265.2HCL (RMT) in VAL cells. RMT improved the sensitivity to apoptosis in EBV- and to some extend in HTLV-1- but not in HHV-8-VAL. Furthermore, we identified that RMT promotes caspase 3 and 9 cleavage by inhibiting XIAP and inducing the mitochondrial efflux of Smac and cytochrome C. This investigation further support exploring the use of Smac inhibitors in VAL.

The use of covalently bonded molecular layers provides a way to combine the outstanding stability and electrochemical properties of carbon-based structures with the unique properties of molecular structures for applications such as electrocatalysis and solar conversion. The functionalization of vertically aligned carbon nanofibers (VACNFs) with 1-alkenes, using ultraviolet light, was investigated as a potential way to impart a variety of different functional groups onto the nanofiber sidewalls. We report how variations in the nanofiber growth rate impact both the amount of exposed edge-plane sites and the resulting electrochemical activity toward Ru(NH3)63+/2+ and Fe(CN)63−/4− redox couples. Measurements of the distribution of surface oxides show that surface oxides are unaffected by the grafting of alkenes to the nanofibers. Carbon nanofiber reactivity was also compared to multiwalled and single-walled carbon nanotubes. Our results demonstrate that edge-plane sites are preferred sites for photochemical g...

We have found that tungsten (W) foils can be used for controlling the carbon diffusion within copper (Cu) enclosures to synthesize large-domain bi-/multi-layer-free monolayer graphene via chemical vapor deposition. We have observed that bi-/multi-layer graphene that nucleate underneath the monolayer graphene can be selectively removed by a W foil placed inside of the Cu enclosure. Both X-ray photoelectron spectroscopy and X-ray diffraction reveal the formation of tungsten sub-carbide (W2C), suggesting the role of the W foil as a carbon sink that alters the carbon concentration inside of the enclosure. Consequently, the bi-/multi-layers appear to dissolve. Utilizing this selective removal process, we were able to demonstrate large-domain (>200 μm) monolayer graphene that is free of any bi-/multi-layers by using Cu double enclosures.

Background Medical students (MS) are increasingly assuming active roles in the operating room. Laparoscopic cases offer unique opportunities for MS participation. The aim of this study was to examine associations between the presence of MS in laparoscopic cases and operation time and postoperative complication rates. Materials and methods Data from the American College of Surgeons National Surgical Quality Improvement Program were linked to operative records for nonemergent, inpatient, and laparoscopic general surgery cases at our institution from January, 2009–January, 2013. Cases were grouped into eight distinct procedure categories. Hospital records provided information on the presence of MS. Demographics, comorbidities, intraoperative variables, and postoperative complication rates were analyzed. Results Seven hundred laparoscopic cases were included. Controlling for wound class, procedure group, and surgeon, MS were associated with an additional 28 min of total operative time. The most significant increase occurred between the skin incision and skin closure. No significant association between the presence of MS and postoperative complications was observed. Conclusions This is the first retrospective analysis to examine the effect of MS presence during laparoscopic procedures. Increase in the operation time associated with the presence of MS should be examined further, to optimize the educational experience without incurring increased cost due to increased operation time.

OBJECTIVES/SPECIFIC AIMS: Evidence-based guideline-concordant care leads to better outcomes in patients with early stage breast cancer, including survival. However, previous studies of guideline compliance have been limited by small study sample sizes, localized geography, unknown causal factors, and lack of diverse population. We use a national database to assess socio-economic, clinical, and facility factors that impact treatment compliance with evidence-based guidelines from the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN). METHODS/STUDY POPULATION: This is a retrospective cohort study of the National Cancer Data Base Participant User File Breast 2014, which captures ~70%–80% of all newly diagnosed cancer cases in the United States. Female patients who were diagnosed with early stage breast adenocarcinoma (T0, T1, T1A, T1B, 2, 2A, or T2N1) from 2004 to 2014 were eligible for this study. RESULTS/ANTICIPATED RESULTS: A total of 807,314 patients were included in this study. Evidence-based guidelines examined with associated compliance rates include surgery completion (79.3% overall compliance), breast conserving surgery Versus mastectomy (88.05% vs. 11.95%, respectively), radiation after breast conserving surgery (77.5% overall compliance), HER2 testing (88.6% overall compliance), estrogen/progesterone receptor (ER/PR) testing (96.3% overall compliance), hormone treatment for positive ER/PR breast cancer (80.2% overall compliance), and sentinel lymph node biopsy completion (67.5% overall compliance). Univariate association between these guidelines and covariates such as facility type, facility location, age, race, insurance status, median income quartiles, achievement of high school degree, urban Versus rural, Charlson-Deyo score, year of diagnosis, and overall survival were assessed. Logistic regression analysis will be used to determine multivariate relationships between these characteristics and the probability that a patient will be compliant to guideline regimen. DISCUSSION/SIGNIFICANCE OF IMPACT: The results of this study will help identify socio-economic, clinical, and facility factors that influence guideline-concordant care and subsequent critical outcomes for patients with early stage breast cancer. Lack of guideline concordant care for specific stages of cancer or treatment modalities will point to a need for tailored interventions to enhance compliance. A prediction model will help identify the most important predictors of noncompliance in breast cancer treatment so noncompliance can be prevented in at-risk populations.

Phase-change materials (PCMs) are promising candidates for nonvolatile data storage and reconfigurable electronics, but high programming currents have presented a challenge to realize low-power operation. We controlled PCM bits with single-wall and small-diameter multi-wall carbon nanotubes. This configuration achieves programming currents of 0.5 microampere (set) and 5 microamperes (reset), two orders of magnitude lower than present state-of-the-art devices. Pulsed measurements enable memory switching with very low energy consumption. Analysis of over 100 devices finds that the programming voltage and energy are highly scalable and could be below 1 volt and single femtojoules per bit, respectively.

The integration of carbon nanotubes with silicon is important for their incorporation into next-generation nano-electronics. Here we demonstrate a non-volatile switch that utilizes carbon nanotube networks to electrically contact a conductive nanocrystal silicon filament in silicon dioxide. We form this device by biasing a nanotube network until it physically breaks in vacuum, creating the conductive silicon filament connected across a small nano-gap. From Raman spectroscopy, we observe coalescence of nanotubes during breakdown, which stabilizes the system to form very small gaps in the network~15 nm. We report that carbon nanotubes themselves are involved in switching the device to a high resistive state. Calculations reveal that this switching event occurs at ~600 °C, the temperature associated with the oxidation of nanotubes. Therefore, we propose that, in switching to a resistive state, the nanotube oxidizes by extracting oxygen from the substrate.

We review recent results concerning reliability and failure (due to heating) of interconnects based on metallic single-walled carbon nanotubes (SWNTs), graphene, and graphene nanoribbons (GNRs). We examine both intrinsic power dissipation within the interconnect as well as extrinsically to adjacent materials. Fundamental reliability limits are different in the diffusive and quasi-ballistic transport regimes. Thermal engineering in the diffusive regime has recently enabled us to reach current densities up to ~4 GA/cm2 for SWNTs and ~2 GA/cm2 for GNRs. However, short carbon-based interconnects (e.g. L

Power consumption and thermal management are significant challenges in electronics, from mobile devices to data centers. A fundamental examination of such aspects could lead to orders of magnitude improvements in energy efficiency. We present recent highlights from our work examining dissipation in nanoscale devices, at contacts, interfaces, and in novel materials. Advances include the use of high-thermal conductivity materials (graphene), low-power data storage (based on phase change rather than charge), and thermoelectric effects for highly localized cooling. Results suggest much room to improve power dissipation in nanoscale electronics, towards fundamental limits, through the co-design of geometry and materials.

Power consumption and heat dissipation are significant challenges in electronics ranging from mobile devices to large data centers. A fundamental examination of energy dissipation in such contexts can lead to orders of magnitude improvements in energy efficiency. We present recent highlights from our work examining power and heat dissipation in nanoscale device geometries, at contacts or interfaces, and when novel materials are involved. For instance, thermal conductivity is significantly reduced in nanostructures due to the role of boundary scattering. However relatively unusual effects such as quasi-ballistic and thermoelectric transport could be used to partially mitigate the heat generated during device operation. In addition, careful low-power device design from the outset can alleviate heat dissipation problems before they begin. For example, data storage based on phase-change (rather than charge) with carbon nanotube electrodes can lead to two orders of magnitude reduction in power dissipation. The results suggest much room to improve power dissipation in nanoscale electronics, towards near-fundamental limits, through the co-design of geometry and materials.

We examine the effect of van der Waals (vdW) interactions between atomic force microscope tips and individual carbon nanotubes (CNTs) supported on SiO2. Molecular dynamics (MD) simulations reveal how CNTs deform during atomic force microscopy (AFM) measurement, irrespective of the AFM tip material. The apparent height of a single- (double-) walled CNT can be used to estimate its diameter up to ∼2 nm (∼3 nm), but for larger diameters the CNT cross-section is no longer circular. Our simulations were compared against CNT dimensions obtained from AFM measurements and resonant Raman spectroscopy, with good agreement for the smaller CNT diameters. In general, AFM measurements of large-diameter CNTs must be interpreted with care, but the reliability of the approach is improved if knowledge of the number of CNT walls is available, or if additional verification (e.g., by optical techniques) can be obtained. Open image in new window

We investigate high-field transport in graphene nanoribbons (GNRs) on SiO2, up to breakdown. The maximum current density is limited by self-heating, but can reach >3 mA/um for GNRs ~15 nm wide. Comparison with larger, micron-sized graphene devices reveals that narrow GNRs benefit from 3D heat spreading into the SiO2, which enables their higher current density. GNRs also benefit from lateral heat flow to the contacts in short devices (< ~0.3 um), which allows extraction of a median GNR thermal conductivity (TC), ~80 W/m/K at 20 C across our samples, dominated by phonons. The TC of GNRs is an order of magnitude lower than that of micron-sized graphene on SiO2, suggesting strong roles of edge and defect scattering, and the importance of thermal dissipation in small GNR devices., this version (v3) is very similar to that ultimately published in PRL

Phase change memory (PCM) is a promising candidate for next-generation non-volatile data storage, though its high programming current has been a major concern. By utilizing carbon nanotubes (CNTs) and graphene as interconnects to induce phase change in ultra small regions (∼20 nm) of Ge 2 Sb 2 Te 5 (GST), we are able to build ultra-low power PCM devices. Normal memory operations are demonstrated with exceptionally low current (< 5 µA) and power consumption, nearly two orders of magnitude lower than state-of-the-art. Electrical characterization shows that switching voltages in PCM with both CNT and graphene electrodes are scalable to sub-1 V. Our experiments also pave the way to carbon nanoelectronics with integrated PCM data storage.

Phase-change materials (PCM) like Ge 2 Sb 2 Te 5 (GST) have been proposed for non-volatile memory and reconfigurable electronics [1, 2]. One of the drawbacks associated with this technology is the relatively high (∼0.5 mA) programming currents required [3]. In this work, we utilize carbon nanotubes (CNTs) as nano-scaled interconnects to induce reversible switching in very small GST bits (∼10 nm). This lowers the programming currents to

We describe a pulsed measurement technique for suppressing hysteresis for carbon nanotube (CNT) device measurements in air, vacuum, and over a wide temperature range (80-453 K). Varying the gate pulse width and duty cycle probes the relaxation times associated with charge trapping near the CNT, found to be up to the 0.1-10 s range. Longer off times between voltage pulses enable consistent, hysteresis-free measurements of CNT mobility. A tunneling front model for charge trapping and relaxation is also described, suggesting trap depths up to 4-8 nm for CNTs on SiO2. Pulsed measurements will also be applicable for other nanoscale devices such as graphene, nanowires, or molecular electronics, and could enable probing trap relaxation times in a variety of material system interfaces.

We study high-field electrical breakdown and heat dissipation from carbon nanotube (CNT) devices on ${\text{SiO}}_{2}$ substrates. The thermal ``footprint'' of a CNT caused by van der Waals interactions with the substrate is revealed through molecular dynamics simulations. Experiments and modeling find the CNT-substrate thermal coupling scales proportionally with CNT diameter and inversely with ${\text{SiO}}_{2}$ surface roughness $(\ensuremath{\sim}d/\ensuremath{\Delta})$. Comparison of diffuse mismatch modeling and data reveals the upper limit of thermal coupling $\ensuremath{\sim}0.4\text{ }\text{W}\text{ }{\text{K}}^{\ensuremath{-}1}\text{ }{\text{m}}^{\ensuremath{-}1}$ per unit CNT length at room temperature, ($130\text{ }\text{MW}\text{ }{\text{K}}^{\ensuremath{-}1}\text{ }{\text{m}}^{\ensuremath{-}2}$ per unit area), and $\ensuremath{\sim}0.7\text{ }\text{W}\text{ }{\text{K}}^{\ensuremath{-}1}\text{ }{\text{m}}^{\ensuremath{-}1}$ at $600\text{ }\ifmmode^\circ\else\textdegree\fi{}\text{C}$ for the largest diameter ($\ensuremath{\sim}$3.2 nm) CNTs. We also find semiconducting CNTs can break down prematurely and display more variability due to dynamic shifts in threshold voltage, which metallic CNTs are immune to; this poses a fundamental challenge for selective electrical breakdowns in CNT electronics.