Extrapulmonary small cell carcinomas (ESCC) are rare but aggressive tumors. Relapses are common despite treatment with chemotherapy and/or radiotherapy. Prospective data for treatment of ESCC are lacking; treatment of these cancers usually incorporates lung small cell carcinoma treatment recommendations. Cancer staging remains the most important prognostic factor. Cancer immunotherapy targeting the PD-1/PD-L1 pathway has shown efficacy in multiple tumor types, and could be an appealing treatment strategy for these rare tumors.We investigated PD-L1 expression by immunochemistry (IHC) in ESCCs diagnosed at University of Massachusetts Medical Center, from 1999 to 2016. 34 cases with sufficient material were selected for PD-L1 IHC analysis using clone E1L3N. PD-L1 expression was evaluated using the combined positive score (CPS). Retrospective chart review was performed. We evaluated the incidence and prognostic value of PD-L1 expression in ESCC at our institution.p-value 0.67). The median overall survival for the PD-L1 positive group, regardless of stage, was 11.5 months versus 7 months for PD-L1 negative group . Patients with limited stage disease with positive PD-L1 had a median survival of 53 months compared to 15 months for patients with PD-L1 negative limited stage .Twelve out 34 cases (35%) had PD-L1 CPS scores ≥1. Ten cases had CPS scores ranging 1–5, whereas 2 cases had CPS scores > 80. The overall response rate to the standard chemotherapy with/without radiotherapy in the PD-L1 positive group was 80% versus 67% for the PDL-1 negative group (This study showed that at least one third of our ESCC tissue samples expressed PD-L1. There was a trend for higher response rates to the standard chemotherapy with/without radiotherapy and improved survival in PD-L1 positive patients. Further studies are required to understand the implications of immune dysregulation in these aggressive tumors. PD-L1/PD-1 inhibitors should be investigated in this group of patients. Extrapulmonary small cell carcinomas (ESCC) have an aggressive nature characterized by early, widespread metastases. These cancers are rare with a reported incidence of 0.1 to 0.4% in North America and represent up to 5% of all cases of small cell carcinoma .Disease stage, either limited or extensive, remains the most important prognostic factor for these cancers . Site ofMost treatment recommendations are derived from small single-institution experiences or extrapolated from pulmonary small cell cancer as prospective trials are lacking for this disease , 6. MultCancer immunotherapy targeting the PD-1/PD-L1 pathway is not yet established for ESCC. We evaluated the incidence and the prognostic value of PD-L1 expression in ESCC at our institution. To our knowledge no studies have investigated the value of PD-L1 testing in ESCC.Institutional review board (IRB) approval was obtained. We investigated PD-L1 expression by immunochemistry (IHC) in ESCC diagnosed at University of Massachusetts Medical Center between 1999 and 2016. Forty-five patients with ESCC were identified. From these patients, 34 had specimens with sufficient material for PD-L1 IHC analysis. Specimens included cytology cell blocks, needle core biopsies, and whole tissue sections from resection specimens.Patients included for analysis had a pathologic diagnosis of ESCC and no evidence of lung disease based on chest CT scan at time of diagnosis. Pathologic diagnosis included morphology consistent with small cell carcinoma, and/or positive immunohistochemical staining with synaptophysin, chromogranin, and/or CD56. Well-differentiated neuroendocrine tumors, including carcinoid tumors, were excluded. Disease stage was classified as extensive (ED) or limited (LD), using the Veterans’ Affairs Lung Study Group criteria, by reviewing radiologic records . LD was Immunohistochemical studies were performed on 5-um sections of formalin-fixed, paraffin-embedded tissue. Slides were first deparaffinized, and rehydrated. Antigen retrieval was carried out with 0.01 M citrate buffer at pH 6.0. Slides were heated in a 770-W microwave oven for 14 min, cooled to room temperature, and rinsed in distilled water before staining. All the slides were stained on the Dako Autostainer . The sections were first blocked for endogenous peroxidase activity with an application of Dual Endogenous Block (Dako) for 10 min, followed by a brief buffer wash. The slides were then incubated with primary antibody for 30 min. The rabbit monoclonal antibody to PD-L1  was used at a dilution of 1:500, and diluted with Dako Antibody Diluent (Dako). Following a buffer rinse, sections were incubated with Ultraview Detection  for 30 min. The sections were washed, and treated with a solution of diaminobenzidine and hydrogen peroxide (Dako) for 10 min, to produce the visible brown pigment. After rinsing, a toning solution  was used for 2 min to enrich the color. Following rinsing, the sections were counterstained with hematoxylin, dehydrated, and cover slipped with permanent media. Sections of tonsil, placenta, and classical Hodgkin lymphoma tissue with known positivity for PD-L1 were used as positive controls for staining.PD-L1 IHC scoring was performed using the combined positive score (CPS), previously described for the scoring of PD-L1 in esophageal adenocarcinoma , 13. CPSp > 0.05 accepted as statistically significant.All survival and subgroup analyses were performed using GraphPad Prism software, with curve comparisons performed using log-rank (Mantel-Cox) tests. Kaplan-Meier survival curves were generated using GraphPad Prism software. Response rates to treatment were compared using Fisher test with Demographic characteristics of the patients and the site of origin of their cancers are shown in Table Twelve specimens (35%) showed positive PD-L1 expression  [Table p-value 0.34) [Fig. p-value 0.80) [Table p-value 0.50).All patient with limited stage received a bimodality treatment with chemoradiation. Fifty-six percent of extensive stage patients received chemotherapy. One patient received platinum and irinotecan, while all other patients with extensive disease who received chemotherapy were treated with platinum and etoposide. The other 46% of patients with extensive stage disease received only supportive care with no chemotherapy; 15% of those patients declined chemotherapy, 9% expired before obtaining the final pathology read but received supportive care while in the intensive care unit, and the remainder had very poor performance status with advanced age. Fifteen percent patients had surgical resection of their primary cancer, in the setting of a diagnostic evaluation. The overall response rate in the PD-L1 positive group was 80% versus 67% in the PD-L1 negative group (7) Table . The med34) Fig. . PatientOf the 25 patients who relapsed, 14 patients relapsed after 2007 when the FDA approved Topotecan for relapsed small cell carcinoma of the lung. Two Patients declined additional chemotherapy, two patients received Topotecan without any response and the remaining 10 patients progressed rapidly and didn’t get treated due to poor performance status. None of the patients received second line chemotherapy before 2007.Our data showed that 35% of ESCC tumor samples were positive for PD-L1(CPS ≥1). PD-L1 positive tumors showed a trend toward improved median overall survival and there was separation of survival curves between the PD-L1 positive and negative groups at around 1 year, though not statistically significant.Treatment of ESCC tends to follow the treatment plan utilized for small cell lung cancer. First line treatment with platinum-based chemotherapy remains the standard. Second line treatments are lacking for all patients with small cell carcinomas, regardless of tissue of origin, with topotecan as the only FDA approved drug in the second line setting . ImmunotPD-1/PD-L1 inhibition has shown efficacy in a variety of malignancies in both first line and subsequent therapy –19. ManyTumor PD-L1 status may provide prognostic or predictive information. A recently published clinical trial conducted in patients with advanced non-squamous, non-small-cell lung cancer, demonstrated a higher response rate to chemotherapy in patients whose tumors had high expression of PD-L1 compared to patients whose tumors failed to express PD-L1 , 22. SimThe proposed rational of improved responses in patients with PD-L1 expression could be related to the presence of lymphocytes at the microenvironment of the tumor cells which could be of help to initiate apoptosis and inflammatory reaction, thus enhancing tumor response to chemotherapy and radiation. It is possible that the enhanced cytotoxicity of combination therapy could be due to the release of tumor neoantigens from cells killed by chemotherapy. Combining immunotherapy with chemotherapy as an upfront treatment is of interest at this point for all small cell carcinomas as chemotherapy showed the potential to increase the PD-L1 expression within the tumor microenvironment, which will enhance the responses to PD-1 inhibitors –25.In conclusion, this study demonstrates the incidence of PD-L1 expression in a small cohort of ESCC, and suggests that PD-L1 expression in ESCC may be of prognostic and predictive relevance. Further studies are required to understand the implications of immune dysregulation in these aggressive tumors. PD-L1/PD-1 inhibitors should be investigated in this group of patients given the positive expression of PD-L1 in one third of patients in our review.


An energy gap can be opened in the spectrum of graphene reaching values as large as 0.2 eV in the case of bilayers. However, such gaps rarely lead to the highly insulating state expected at low temperatures. This long-standing puzzle is usually explained by charge inhomogeneity. Here we revisit the issue by investigating proximity-induced superconductivity in gapped graphene and comparing normal-state measurements in the Hall bar and Corbino geometries. We find that the supercurrent at the charge neutrality point in gapped graphene propagates along narrow channels near the edges. This observation is corroborated by using the edgeless Corbino geometry in which case resistivity at the neutrality point increases exponentially with increasing the gap, as expected for an ordinary semiconductor. In contrast, resistivity in the Hall bar geometry saturates to values of about a few resistance quanta. We attribute the metallic-like edge conductance to a nontrivial topology of gapped Dirac spectra. The absence of a bandgap in the electronic spectrum of graphene can be overcome by breaking its lattice symmetry. The authors show that the insulating state of gapped graphene is electrically shorted by narrow edge channels exhibiting high conductivity. Egap can be controlled by the displacement field D applied between the two graphene layers. Large gaps were found using optical methodsT) dependences of resistivity ρ at sufficiently high T , ρ at the charge neutrality point (CNP) in gapped graphene is often found to saturate to relatively low values that are incompatible with large Egap  are protected by symmetry of their crystal lattices. If the symmetry is broken by interaction with a substrate13h T refs , 9, 10. gap refs . This diL varying from 300 to 500 nm and the width W from 3 to 5 μm. To ensure highest possible quality2 substrate as a bottom gate  in the x direction perpendicular to the supercurrent flow can be deducedJs(x) changes with opening the gap.We start with discussing behaviour observed for superconductor-graphene-superconductor (SGS) Josephson junctions. Our devices were short and wide graphene crystals that connected superconducting Nb electrodestom gate . For detVtg and Vbg, respectively), it is possible to keep BLG charge neutral while doping the two graphene layers with carriers of the opposite sign  that translates directly into the spectral gap345Egap(D) can be deduced not only theoretically but also measured experimentally, as discussed in section 1 of Ic as the current at which the differential resistance dV/dI deviates from zero above our noise levelIc corresponds to the edge of the dark area outlined by bright contours. At high doping (Fermi energy >Egap) and low T, Ic is found to depend weakly on D, reaching values of a few μA μm−1, in agreement with the previous reports2224Egap  reaching ≈300 nA for the junction shown in D=±0.07 V nm−1, which corresponds to Egap≈7 meV. For larger gaps, Ic becomes smaller than 1 nA and could no longer be resolved because of a finite temperature (down to 10 mK) and background noiseBy varying the top and bottom gate voltages (sign see . This re2224Egap . AccordiIc(B), with increasing D . At zero D, we observe the standard Fraunhofer pattern at the CNP, which is basically similar to that measured at high doping . The phase of the oscillations changes by 90° and the central lobe becomes twice narrower. In addition, the side lobes no longer decay with increasing B but exhibit nearly the same amplitude , which yieldedJs(x) shown in D=0.025 V nm−1 but further increase in D suppresses the bulk current to practically zero, within the experimental accuracy of our FFT analysis  and gapless  MLG. In the gapped device, the supercurrent is suppressed not only at the main CNP but also at secondary CNPs. For all electron and hole concentrations away from the CNPs, both devices exhibit the standard Fraunhofer pattern indicating a uniform supercurrent flow  results in opening of a gap of ≈30 meV at the main CNP–2° resul12010 cm−2 . The fig11 cm−2) and were observed for devices with the top gate being only a few nm away from the graphene plane. The latter facilitates a uniform electric field distribution 2122ribution . Chemicaribution . We alsoribution . The latEgap such that junction's resistance remains well below 1 MOhm allowing superconducting proximity. To address the situation for the larger gaps accessible in BLG devices, we compare their normal transport characteristics in the Corbino and Hall bar geometries. Because the Corbino geometry does not involve edges, such a comparison has previously been exploited to investigate the role of edge transport  as expected for a semiconductor with the gap Egap  found using the Hall bars rapidly saturated below 100 K to values of a few resistance quantum RQ=h/e2 and changed little (by <30%) with decreasing T down 2 K. The saturation behaviour is similar to that observed for conductance along a p–n junction in oppositely biased BLGAnother noteworthy distinction between the two geometries is their temperature dependences at the CNP. For gap Egap . Our meaξ is very long with respect to the lattice constant a. For MLG and BLG, ξ can be estimated as ≈ħv/Egap and ħ/ħ is the reduced Planck constant, v the Fermi velocity in MLG and m the effective mass in BLG. For our typical gaps, ξ is about 10–20 nm, much larger than a. This suggests that wavefunctions of isolated zigzag states should strongly overlap inside the bulk creating a quasi-one-dimensional band. Moreover, because ξ/a≫1, the wavefunctions mostly reside in the bulk where there are little defects, which ensures that impurity bands are effectively protected against backscattering. The situation resembles the modulation doping used to achieve high-carrier mobilities in semiconductor quantum wells. The observed saturation of ρ to ∼RQ and the long-range nonlocal resistance reported previously1617T localization lengths at least an order of magnitude shorter than this scale, localization in the edge channels may be suppressed by a finite T and electron–electron interactions that are prominent especially in low-dimensional conductors. Such delocalization effects have so far not been investigated theoretically. The invoked edge channels would be consistent with our experimental observations. Obviously, the mean free path can vary from sample to sample and strongly depend on fabrication procedures, which may explain only weakly saturating behaviour that was reported in some gapped graphene devices16171322Two possible scenarios for shunting the insulating state of gapped graphene have previously been put forward. Both rely on nontrivial topology of the gapped Dirac spectrum. One of them considers electronic states due to short zigzag segmentsOur results can explain low apparent resistivity often observed for charge-neural gapped graphene at low temperatures, especially in devices made from high-quality graphene in which the bulk is expected to contribute little to either hopping conductivity or backscattering of edge modes5678910112) and then annealed at 300 °C in a forming gas (Ar–H2 mixture) for 3 h. As the next step, we used the standard electron-beam lithography to create a poly (methyl methacrylate) (PMMA) mask that defined contact regions. Reactive ion etching (Oxford Plasma Lab 100) was employed to make trenches in the heterostructure through the mask. We used a mixture of CHF3 and O2, which provided easy lift-off of PMMA, so that metal contacts could be deposited directly after plasma etching. This also allowed us to minimize contamination of the exposed graphene edgesMono- or bilayer graphene crystals were encapsulated between hBN crystals  using the dry transfer technique as detailed previouslyT down to 0.3 K and, for lower T, in a dilution refrigerator with the base temperature of 10 mK (BlueFors Cryogenics). The differential resistance was measured in a quasi-four-terminal configuration (two superconducting leads for driving the current and the other two for measuring voltage) using a low-frequency lock-in technique. All electrical connections to our devices passed through a cold RC filter (Aivon Therma) placed close to the sample and additional AC filters were used outside the cryostats. At large displacement fields, our Corbino devices exhibited high resistivity such that the lock-in technique became inappropriate. In this case, we used dc measurements.All electrical measurements were carried out in a He3 cryostat (Oxford Instruments) for The data that support the findings of this study are available from the corresponding author upon request.How to cite this article: Zhu, M. J. et al. Edge currents shunt the insulating bulk in gapped graphene. Nat. Commun.8, 14552 doi: 10.1038/ncomms14552 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary Figures, Supplementary Notes and Supplementary References


A rare case of ovarian sarcoidosis with peritoneal and omental involvement presenting as an ovarian malignancy is presented. Clinical, laboratory, and radiological evaluation of the patient revealed ascites and high levels of serum CA 125 and CA 15.3. The diagnosis of sarcoidosis was confirmed with pathology findings on tissues obtained during surgical laparotomy. Establishing the diagnosis of sarcoidosis can be treacherous and was complicated in this case by the falsely elevated biomarkers and ascites. Atypical manifestations of sarcoidosis occurring outside typically affected organs make histology necessary in establishing the diagnosis after excluding infectious and neoplastic mimics of the disease. Extrapulmonary sarcoidosis has been reported in several sites; however localization of the disease in the female reproductive system is extremely rare accounting for less than 1% of cases [A 79-year-old, gravida 4, para 2, Caucasian female with a history of weight loss and fatigue for 4 months was referred to our hospital for investigation of her symptoms. Medical history was significant for dyslipidemia and hypertension treated with irbesartan. The physical examination disclosed no abnormalities. Due to concern for malignancy, diagnostic imaging was performed. Chest X-ray was negative. Ultrasound, CT, and MRI of the abdominal area showed the presence of minimal amounts of free liquid in the perihepatic area, in the paracolic sulci, in the right inguinal region, and in the pouch of Douglas, without the involvement of retroperitoneal, paraaortic, and iliac chain lymph nodes. Since the suspicion of malignancy remained high, the gynaecology team ordered cancer biomarkers; testing disclosed a CA 125 value of 225.20 U/ml  and a CA 15.3 value of 73.9 U/ml . Levels of carcinoembryonic antigen were within normal range; that is, CEA levels were 1.43 ng/ml  and carbohydrate antigen 19-9 (CA 19-9) levels were 6,4 U/ml . Cytological examination of the ThinPrep® sample obtained via a transvaginal fine-needle aspiration was negative for malignancy only disclosing an abundance of histiocytes, lymphocytes, white blood cells, and few mesothelial and red blood cells. An exploratory laparotomy was performed; multiple grey-white miliary nodular lesions with a diameter ranging from 0.2 to 1.6 cm were observed on the surface of the left ovary, the uterus, the peritoneum, the omentum, and the small and large intestine. Histological examination of omental and peritoneal biopsies disclosed the presence of noncaseating, nonnecrotic, sarcoid type granulomas containing multinucleated giant cells Figures  containiThe final histological diagnosis was granulomatous, sarcoid type inflammation. Evaluation by an expert pulmonologist revealed no evidence of lung sarcoidosis by CT scan and gallium scanning. The patient was further investigated in the direction of possible extra pulmonary involvement with no abnormal findings revealed. A decision to withhold further therapy was made. The patient is doing well after one year of follow-up without other complications.There was neither family history of sarcoidosis, nor history of immunodeficiency or biological factor therapy. Furthermore, the patient did not mention any occupational or environmental exposure in industrial work associated with beryllium; such exposure has been associated with granuloma formation, pulmonary sarcoidosis, and elevations of Serum Angiotensin-Converting Enzyme (SACE) activity . No histHistology confirmation is necessary for the diagnosis of sarcoidosis occurring outside usually affected organs, for example, the lung. In any case the physician needs to exclude the presence of infectious or neoplastic mimics of the disease. Sarcoidosis has been very rarely described to affect the female genital tract especially the ovaries and even more rarely in relation to a concomitant malignancy –7.In our case peritoneal involvement was also noted which has been described more frequently –10. In sWith regard to the elevated biomarkers the abnormal CA-125 levels are explained by the presence of peritoneal involvement and ascites and have been previously described , 16. It In our report surgical intervention led to the correct diagnosis. Similarly, in previous reports, a provisional diagnosis of ovarian malignancy was excluded by exploratory laparotomy and histological confirmation of sarcoidosis , 13, 19.In conclusion, we describe a rare case of ovarian, peritoneal, and omental sarcoidosis with no lung involvement and abnormally elevated CA 15-3 levels. Cancer biomarkers should not be used to exclude or confirm the diagnosis of cancer or sarcoidosis for the same matter. In our case their use misled the physicians in assuming the presence of a gynecological malignancy. Histological confirmation of the diagnosis is necessary in such difficult cases.


Electrical generation and detection of pure spin currents without the need of magnetic materials are key elements for the realization of full electrically controlled spintronic devices. In this framework, achieving a large spin-to-charge conversion signal is crucial, as considerable outputs are needed for plausible applications. Unfortunately, the values obtained so far have been rather low. Here we exploit the spin Hall effect by using Pt, a non-magnetic metal with strong spin-orbit coupling, to generate and detect pure spin currents in a few-layer graphene channel. Furthermore, the outstanding properties of graphene, with long-distance spin transport and higher electrical resistivity than metals, allow us to achieve in our graphene/Pt lateral heterostructures the largest spin-to-charge output voltage at room temperature reported so far in the literature. Our approach opens up exciting opportunities towards the implementation of spin-orbit-based logic circuits and all electrical control of spin information without magnetic field. Spintronic devices with full electrical control rely on electrical generation and detection of spin currents in the absence of magnetic materials. Here, the authors use Pt, a non-magnetic metal, to generate and detect pure spin currents in a few-layer graphene channel, achieving a remarkable spin-to-charge voltage signal at room temperature. In particular, in the emerging field of spin orbitronics10, by uniquely exploiting the spin-orbit coupling (SOC) in non-magnetic materials, spin-to-charge current conversions have been realized using the spin Hall effect (SHE)13, the Rashba–Edelstein effect15, or the spin-momentum locking in topological insulators17. Magnetization switching of FM elements for memories7 or the recent proposal of a scalable charge-mediated non-volatile spintronic logic18 are applications based on SOC, which can have a strong technological impact.A spintronic device with complete electrical functionality is attractive for its incorporation into the current charge-based integrated circuits. While advances have been made in the electrical control of spin transport19. The efficiency of this spin-to-charge interconversion is given by the spin Hall angle (θSH). As technological applications require large conversions, finding routes to maximize θSH has become a demanding task. The materials with highest reported yields are heavy metals with strong SOC, such as Pt21, Ta5 and W23. Recently, a clear route to enhance θSH of Pt has been unveiled21. Another path that has been explored to maximize the output voltage is the use of higher resistive spin Hall materials, although the potential enhancement is counteracted by the increased shunting of the induced charge current in the less resistive spin transport material, usually Cu or Ag8. It would be desirable to employ these spin-to-charge conversions to efficiently inject and detect pure spin currents in good spin transport materials with higher charge resistance.In the SHE, a pure spin current is generated from a charge current owing to the strong SOC in a non-magnetic material. Reciprocally, the inverse spin Hall effect (ISHE) can be used for spin detection, as a spin current is turned into a measureable charge current24, is theoretically predicted and experimentally demonstrated to be an excellent material for spin transport40. Spin diffusion lengths of up to 90 μm have been reported at room temperature32, a parameter found to be fairly insensitive to temperature39. However, electrical spin injection from FM sources suffers from a lack of reproducibility owing to the required interfacial barriers40, which are usually made of oxides that grow in an island mode on the graphene surface. An efficient and reliable spin injection and detection into such an outstanding spin transport material at room temperature using non-magnetic electrodes is of both fundamental and technological interests.Graphene, due to its weak SOCIn our work, we demonstrate the generation (detection) of a pure spin current in a graphene-based lateral heterostructure by employing the SHE (ISHE) of Pt, avoiding the use of a FM source. Moreover, the large charge resistance of graphene as compared to the standard spin transport metals such as Cu and Ag eliminates completely the shunting effect, generating large output voltages. The spin-to-charge conversion signal in a graphene/Pt lateral device at room temperature is two orders of magnitude larger than the best performing ones previously reported that use metallic channels. Our concept of using charge-to-spin conversion to inject a spin current and spin-to-charge conversion to detect a spin currents in graphene-based devices could open future applications of all electrical control of spin information without magnetic field.n ~ 8 × 1011 cm−2) obtained via exfoliation41, where spins are to be transported. Several ferromagnetic Co electrodes with their respective TiO2 interfacial barriers are placed on top of the flake. The presence of TiO2 between the Co electrode and the graphene channel leads to interface resistances between 10 and 42 kΩ. In addition, Pt wires are placed on top of the graphene channel. We use very resistive Pt with ρPt = 99 (134) µΩcm at 50 (300) K and, therefore, a large spin Hall angle of θSH = 17.8 ± 2.0 (23.4 ± 2.5)%21. Transport measurements are performed in a liquid-He cryostat with a superconducting magnet using a DC reversal technique44. See Methods for details on the device fabrication and measurements.We used the spin absorption method in lateral spin valve (LSV) devices to demonstrate spin generation and detection in graphene via the SHE and ISHE of Pt, respectively  is injected from a Co electrode into the graphene channel, creating a spin accumulation at the Co/graphene interface. This spin accumulation diffuses toward both sides of the graphene channel, creating a pure spin current, which is detected by another Co electrode as a nonlocal voltage (VNL), see Fig. RNL = VNL/IC is high (x direction (Bx) owing to the shape anisotropy of the electrodes . In this case, the pure spin current injected from the Co electrode diffuses along the graphene channel and is mostly absorbed by the Pt wire. In the Pt wire, owing to the ISHE, a charge current perpendicular to both the spin current direction and the spin polarization is created  and, thus, a voltage drop is generated along the Pt wire. The measured voltage normalized to the injected current IC yields the ISHE resistance, RISHE. By sweeping the magnetic field (By) from positive to negative, the magnetization of the Co electrode (as well as the orientation of the spin polarization) rotates, and RISHE reverses sign as shown by the blue curve in Fig. θ13, a value which has been extracted from the Hanle data . The transverse spin current generated in Pt by the SHE has a spin polarization oriented along the y axis, and the spin accumulation in the graphene/Pt interface leads to spin injection into graphene . By employing now the Co electrode as a detector, we are able to measure the pure spin current reaching the Co electrode as a voltage, obtaining the corresponding SHE resistance, RSHE, after normalizing by IC =RISHE(−By) by swapping the voltage and current probes with the same polarity   2) the ementclass2pt{minimλGr ~ 1.2 µm) and its temperature insensitivity. Graphene’s exceptional ability to transport spins remains intact at room temperature, that is, the same amount of spin current arrives to the Pt absorber at different temperatures; Second, although the amount of spin current to be converted remains the same, the efficiency of the conversion (θSH) of Pt increases linearly with temperature from 17.8 ± 2.0% at 50 K to 23.4 ± 2.5% at 300 K21; Third, the resistivity of Pt increases from 99 µΩcm at 50 K to 134 µΩcm at 300 K; and fourth, the negligible shunting of the charge current in Pt by graphene (xPt/Gr ≈ 1). The enhancement of ΔRSCC with increasing temperature mainly benefits from the first three factors, which are constant λGr and increasing θSHρPt product as described in eq  and fourth (negligible shunting) factors. In traditional metallic LSV devices, the resistivity of the metal channel is close or smaller than that of the spin Hall metal, thus x are much lower (0.05–0.36)52, a serious issue preventing large spin-to-charge conversion pointed out recently8. However, in our device with few-layer graphene/Pt heterostructure, xPt/Gr≈1 is close to ideal and the use of more resistive graphene (single or bilayer) is not necessary, as xPt/Gr cannot be further increased. Further improvement to the spin-to-charge conversion could be easily achieved by using high quality graphene devices, where almost two orders of magnitude enhancement of λGr is obtained32, or reducing the spin current dilution into the Pt wire by decreasing its thickness  is not appropriate, because they quantify different outputs. Whereas the former only probes the spin accumulation in the channel through a ferromagnetic tunnel barrier and acts as spin detector, the latter is a measurement of the converted charge current through a transparent interface, which can be potentially utilized  and identified using its optical contrast41. We select flakes with the most convenient shape (long and narrow), regardless of the number of layers, as the excellent spin transport properties do not depend strongly on the number of graphene layers36. The nanofabrication of the device follows two steps of e-beam lithography with electrode metal deposition and lift-off. For the 200-nm-wide Pt wires, 21 nm of Pt were sputtered at 0.6 Ås−1 using 40 W in 3 mTorr of Ar pressure. This deposition condition gives rise to very resistive Pt with ρPt = 99 (134) µΩcm at 50 (300) K. The 35-nm-thick Co electrodes with widths between 150 and 350 nm are deposited in an ultra-high vacuum chamber using e-beam evaporation on top of 6 Å of Ti after the natural oxidation of Ti in air. The presence of TiO2 between the Co electrode and the graphene channel leads to interface resistances between 10 and 42 kΩ.To fabricate our devices, few-layer graphene flakes are first produced by micromechanical cleavage of natural graphite onto 300-nm-thick SiO44.The measurements are performed in a Physical Property Measurement System by Quantum Design, using a DC reversal technique with a Keithley 2182 nanovoltmeter and a 6221 current sourceAll relevant data are available from the authors.Supplementary InformationPeer Review File


As cathode materials for lithium-ion batteries, the nanosheet-assembled V2O5/graphene composite exhibits better rate capability and long-term cycling stability. The V2O5/graphene composites can deliver discharge capacities of 133, 131, and 122 mAh g−1 at 16 C, 32 C, and 64 C, respectively, in the voltage range of 2.5–4.0 V vs. Li/Li+. Moreover, the electrodes can retain 85% of their original capacity at 1C rate after 500 cycles. The superior electrochemical performances are attributed to the porous structures created by the connected V2O5 nanosheets and the electron conductivity improvement by graphene.Transition metal oxides and graphene composites have been widely reported in energy storage and conversion systems. However, the controllable synthesis of graphene-based nanocomposites with tunable morphologies is far less reported. In this work, we report the fabrication of VThe online version of this article (doi:10.1186/s11671-016-1764-3) contains supplementary material, which is available to authorized users. Rechargeable lithium-ion batteries, as one of the most important energy storage devices, have been widely used in consumer electronic devices such as cell phones, laptop computers, and hybrid electrical vehicles. However, the increasing demands for better batteries push the researchers to develop new electrode materials with improved performance including higher energy density, better rate capability, and longer lifespan –3.2O5 is a promising material because of its low cost, abundant resource reservation, and high-energy density [−12–10−13 cm2 s−1) and moderate electrical conductivity (10−12–10−13 S cm−1) limit its electrochemical performance [2O5 nanomaterials, such as nanorods [2O5 is still undressed. More recently, making V2O5 nanocomposites with conductive materials are effective for obtaining high-performance electrode materials. In particular, carbonaceous materials such as carbon nanotubes [2@graphene [2O3@graphene [3O7@graphene [Among the numerous cathode materials, V density . Howevernanorods , nanotubnanorods , nanowirnanorods , nanoshenanorods , 10, nannanorods –13, and nanorods , 15 wereanotubes , 17, mesanotubes , and graanotubes , 19, 20 anotubes –23. In tgraphene , V2O3@grgraphene , and V3Ographene , have be2O5/graphene with different morphologies by a solvothermal approach with subsequent annealing in air. Vanadium precursors with nanosheet or nanoparticle morphology are controllably prepared on the surface of graphene and can be converted into V2O5/reduced graphene oxide nanocomposites with good structural reservation in the calcination process in air. As cathode materials for lithium-ion batteries, the nanosheet-structured V2O5/reduced graphene oxide nanocomposites exhibit much better rate capability and cyclic stability than V2O5 nanoparticles/reduced graphene oxide composites. The relationship between nanostructures and their electrochemical performance is discussed.Herein, we report the structural engineering of V2O5/reduced graphene oxide composite I (V/GO-I).The graphene oxide was made by a modified Hummers method . For the2O5/graphene composite was prepared by adding extra 2 mL deionized (DI) water into the solvothermal solution, keeping other parameters unaltered. The obtained material was designated as nanoparticle-structured V2O5/reduced graphene oxide composite II (V/GO-II).The nanoparticle-assembled Vλ = 1.54178 Å) using a step of 0.02o between 10° and 80° (2θ). The morphologies of the samples were studied by scanning electron microscopy  and transmission electron microscopy . The X-ray diffraction (XRD) patterns of the samples were collected in the range between 10o and 80o with a step size of 0.02°. The weight percentages of graphene in the V2O5/graphene composites were determined by thermogravimetric (TG) analysis with a heating rate of 10 °C min−1. A spectrometer  with a back-illuminated charge-coupled detector attachment was used to record the Raman spectra.The crystal phases were collected using a Rigaku D/max2500 with Cu-Kα radiation  in a weight ratio of 70:20:10 was dispersed in an N-methyl-2-pyrrolidone (NMP) solution to make a slurry, which was coated on aluminum foil and dried in a vacuum oven at 100 °C overnight. The cells were assembled in the glove box  filled with ultra-high-purity argon using polypropylene membrane as the separator, lithium metal as the anode, and 1-M LiPF6 in ethyl carbonate/dimethyl carbonate (1:1 v/v) as the electrolyte. The cyclic voltammetry (CV) measurement was tested on CHI660C , and the galvanostatic discharging/charging experiment was tested on a Land battery tester . The measurements were all carried out in the voltage range of 2.5–4.0 V (vs. Li/Li+). The electrochemical impedance spectrometry (EIS) was carried out on a ZAHNER-IM6ex electrochemical workstation (ZAHNER Co. Germany) in the frequency range of 100 kHz to 10 mHz using the fresh cell.The electrochemical performances of the electrodes were tested in a coin cell assembly (2016 type coin cell). For the electrode preparation, a mixture of V2O5/graphene nanocomposites with diverse self-assembled subunits. As indicated by process I, vanadium precursor nanosheets are grown on the graphene nanosheets first during the solvothermal process, in which vanadium triisopropoxy oxide (VO(OiPr)3) was used as the vanadium resources. The prepared vanadium precursor and graphene composite can be converted into V2O5 and graphene composite with well-preserved structures. Process II indicates the preparation of nanoparticle-assembled vanadium precursor and graphene composite by adding extra 2 mL de-ion water in the solvothermal solution. Thereafter, the precursor composite can be converted into V2O5 nanoparticles and reduced graphene oxide nanocomposites (V/GO-II).Figure 2 phase (space group: P42/mnm (136); a = 0.4556 nm, b = 0.4556 nm, c = 0.285 nm, JCPDS card no. 76-0677). The formation of VO2 phase can be attributed the reduction of V2O5·nH2O by alcohol during solvothermal process, in which V2O5·nH2O is prepared by the hydrolysis of vanadium triisopropoxy oxide with water. The result indicates the structures of the vanadium precursor can be adjusted by the addition of 2 mL de-ion water. The addition of water can speed the hydrolysis reaction between vanadium triisopropoxy oxide and water to form brown colored V2O5·nH2O, which may generate more nucleation on the graphene nanosheets, but sacrificing their parcel growth. However, due to the amorphous feature of the vanadium precursor nanosheets, it is difficult to give the exact reaction during the solvothermal process. The formation of the amorphous nanosheets may be attributed to the decomposition of vanadium triisopropoxy oxide under the condition of high temperature and high pressure during the solvothermal process. Much less nuclei seeds are formed on the reduced graphene oxide and grow continuously to form the nanosheet morphology without the addition of water.Figure 2O5 phase (space group: Pmmn (no. 59); a = 1.1516 nm, b = 0.3565 nm, c = 0.4372 nm, JCPDS card no. 41-1426). The existence of reduced graphene oxides in the composite was confirmed by the Raman results, as shown in Fig. −1 correspond to the typical G and D bands of graphene. Moreover, the intensity ratio between G and D bands become larger, indicating the partial reduction of graphene oxide. All other Raman peaks for the V/GO-I composite and the V/GO-II composite can be characterized on the basis of the vanadium oxide  for V/GO-II composite. The corresponding charge/discharge curves are shown in Additional file −1 at 16C, 32C, 40C and 64C, respectively. When the discharge/charge rates were reset to 1C, high discharge capacity of 139 mAh g−1 can be recovered for both composites. The coulombic efficiency of V/GO-I composite is close to 100% in the whole discharge/charge process.Figure 2O5/graphene composite, which may be attributed to the porous structures created by the nanosheets.Figure 2O5/graphene composites. The V/GO-I composite deliver an initial high specific capacity of 142 mAh g−1 at 2C and retain a capacity of 121 mA h g−1 after 500 cycles. The average capacity fading is only 0.03% per cycle. For comparison, the V/GO-II composite only retains a capacity of 80 mA h g−1 after 500 cycles at the same rate. Additional file −1, respectively, for the V/GO-I composite and the coulombic efficiency can be of 99.6%. After 500 cycles, the plateaus can still be easily detected. Additional file Figure 2O5 and reduced graphene oxide composite. According to the electrochemical analysis results, the nanosheet-assembled V2O5/graphene composite exhibit better rate capability, cycling stability, and lower charge transfer resistance than the nanoparticle-assembled V2O5/graphene composite. The electrochemical performance of V/GO-I composite is also much better than many previously reported V2O5 electrodes, such as hollow structured V2O5 microspheres [2O5 [2O5-based electrodes in this work and from many previous reported literatures. As shown in Table 2O5/r-GO composite exhibit higher capacity and better rate capability than many other V2O5-based electrodes. The excellent rate performance and superior cyclic stability can be attributed to the synergistic effects between V2O5 and graphene substrates, which include the following aspects: (1) the growth of V2O5 nanosheets on reduced graphene oxide can ensure the good electronic conductivity of the electrode materials; (2) the porous space created by the interconnected large nanosheets can improve the accessibility of the electrolyte with the electrode materials; (3) the ultra-thin nanosheet thickness can greatly reduce the Li+ ions diffusion and electron transportation distances; and (4) the porous structure may better accommodate the volume changes upon cycling.Figure ospheres  and threres [2O5 . Table 22O5/reduced graphene oxide composites are synthesized by adjusting the solvothermal condition. The vanadium precursor can grow homogeneously on the reduced graphene oxides and the obtained composites can be converted into V2O5/reduced graphene oxide composites with good structural reservation. As cathode materials for lithium-ion batteries, the nanosheet-assembled V2O5/reduced graphene oxide nanocomposites (V/GO-I) exhibit better rate capability and cycling stability than the nanoparticle-assembled V2O5/graphene nanocomposites (V/GO-II). The superior electrochemical performance is attributed to the synergistic effects between V2O5 nanosheets and reduced graphene oxides.In summary, nanosheet- or nanoparticle-assembled V


Audience response systems (ARS) are increasingly popular; however, their contribution to education is not completely clear. Our study found that scores from review quizzes delivered by an ARS correlate with in-training exam (ITE) scores and are viewed positively by residents. This information may be useful in identifying poor performers early so that targeted educational interventions can be made. The objective was to determine if scores on review quizzes delivered by an ARS correlate with ITE scores and to obtain participant feedback on use of the ARS for ITE preparation.This was a prospective observational study of emergency medicine (EM) residents at six accredited EM residency programs. Subjects included residents who had taken previous ITEs. Subjects participated in bimonthly review sessions using an ARS. Twelve review quizzes were administered, each consisting of 10 multiple-choice questions. After the ITE, subjects completed an attitudinal survey consisting of six Likert-scale items and one “yes/no” item. We used a mixed linear model to analyze the data, accounting for prior 2012 ITE scores and nesting due to institution.Among 192 participants, 135 (70.3%) completed the ITE in both 2012 and 2013; we analyzed their data for the first objective. Results from the mixed linear model indicate that the total mean score on the review quizzes was a significant  predictor of the 2013 ITE after controlling for the 2012 ITE score. One hundred forty-six (76.0%) participants completed the attitudinal survey; 96% of respondents stated that they would like ARS to be used more often in resident education. Respondents felt the sessions aided in learning (mean 7.7/10), assisted in preparation for the ITE (mean 6.7/10), and helped identify content areas of weakness (mean 7.6/10).Our results suggest that scores from review quizzes delivered by an audience response system correlate with in-training exam scores and is viewed positively by residents. To become board certified, emergency physicians must pass the American Board of Emergency Medicine (ABEM) written and oral certification examinations. In preparation, residents take an annual in-training exam (ITE). EM residencies aim for all residents to pass the written examination. As a result, it is common practice for residencies to dedicate specific didactic time as review sessions to improve ITE scores. The amount and method of this preparation is variable. We sought to develop a curriculum using an audience response system (ARS) that could potentially predict how residents would perform on the ITE.There are a number of ARSs available and they are increasingly used for didactic teaching. They involve wireless technology where participants send a response via keypads, clickers or cell phones to a computer that then tallies and projects those responses to the audience. The audience responses to questions or stimuli can be embedded graphically in a PowerPoint lecture providing immediate feedback to the audience about their input. ARS have been shown to improve the effectiveness of didactic lectures by increasing attendance, attention levels, motivation, participation and engagement.8The literature on ARS is clear that students embrace this technology as a learning tool; however, it remains unclear whether participation and tracking of results through an ARS can assist educators in predicting which students will do poorly on an annual comprehensive exam. If such a system could predict those at risk for poor outcomes, early targeted educational interventions could take place. The primary objective of this study was to determine if the results of bi-monthly, written, board-style questions using the ARS were correlated with the annual ITE scores among EM residents from six different programs. In addition, we wanted to determine resident reactions to the use of an ARS for ITE review.What do we already know about this issue?Learners enjoy the use of an audience response system for didactic education. Whether it is valuable in predicting or improving learning is not entirely clear.What was the research question?Do scores on review quizzes delivered in resident conference using an audience response system correlate with scores on the in-training exam?What was the major finding of the study?Review quizzes delivered by an audience response system are viewed positively by residents, and results correlate with in-training exam scores.How does this improve population health?Improvements in the education of core content to residents will likely improve the quality of care delivered by them in the long run.Residents from six EM residency programs accredited by the Accreditation Council for Graduate Medical Education participated in this study. Collaboration was facilitated through the MERC  at CORD (Council of Residency Directors) Program. The ™ ARS.This prospective, multicenter cohort study was conducted from August 2012 to January 2013. Study participants were all the EM residents at each training site that routinely attend conference. They were all consented for participation. No residents were excluded; however, because first-year residents at Harbor-UCLA Medical Center do not attend didactic conference they were not consented and they did not participate. Although the interns at the other sites did not have prior ITE scores for comparison, they were included in the study because they would be participating in the ARS and completing the post-survey. All participants present for the session answered EM board-style questions during didactic conference twice per month for the six months  preceding the ITE in February 2013. Each program has regular didactics that occur on a weekly basis. Residents who were present for the board review  would voluntarily answer the questions via the audience response clickers. Administration of questions was done by a single person at each institution, using the Turning Point TechnologyTopics were chosen a priori based on the list of most commonly asked question topics published by ABEM on their website.™  is a specific audience response product using audience clickers, which send feedback to a receiver with a USB hub that attaches to the computer. It is completely integrated with PowerPoint such that the slideshow appears identical to what residents are accustomed to seeing. Subjects were given a question and multiple-answer choices on the slide. After everyone clicked their answer selection, a graphic display of the percentage or number of subjects who selected each choice was displayed for everyone to see. Participants were not individually identified. Thereafter, a checkmark appeared informing the audience of the correct answer. There wasn’t a scripted discussion of the correct answers, but the administrator of the questions was allowed to explain why the answer was correct and why the other options were incorrect.Turning Point Technologies™. PowerPoint sessions were then sent to the lead investigator at each site. Sessions were consistently administered by the lead investigators  twice a month for six months to cover the 12 most commonly tested topics. If a session could not be administered in the assigned month, the topic was skipped to ensure all participants completed the questions at the same time in their residency training.One investigator (KS) randomly selected the 10 questions for each topic from the topic-specific pool of questions on the RoshReview website. Questions were then placed in a PowerPoint presentation that allowed for use with Turning Point TechnologiesResidents were assigned particular clickers that they used for each session, thereby maintaining a unique identifier that remained de-identified to the study investigators. The answer choice selected by each participant (and correct or incorrect designation) was automatically recorded with the unique identifier of each participant. At the completion of each session, data automatically generated by the ARS was sent to one investigator (KS) for collection.After the ITE, subjects completed a questionnaire to determine their attitudes toward the review sessions delivered by an ARS. The questionnaire consisted of six 10-point Likert-type items and one “yes/no” item. The questions were developed by the research group with attention to content validity through iterative drafts of the survey. Internal structure and response process validity was supported by adherence to survey design principles, review by an educational research expert, and piloting and revision of survey; consistency was determined by Crohnbach’s alpha of 0.81. See list of questions in To control for prior performance on the ITE, we completed this analysis using only residents who had a 2012 ITE score in addition to a 2013 ITE score. Analysis was performed using a nested mixed linear regression model using SAS version 9.3. We calculated the score on each quiz in terms of the percentage correct, and adjusted the total percentage correct on all tests by the total number of tests taken. Scores from incomplete quizzes, defined as less than 7 out of 10 questions answered, were excluded from analysis. The total ITE score in 2013 was the outcome and it was adjusted for each participant’s 2012 ITE score and the participant’s institution. We included all available demographic variables and the institution in the model. For the attitudinal responses, mean ratings with standard deviations for Likert scale items were calculated using Excel. Response rate for the single “yes/no” question was also recorded.p < 0.0001] predictor of the 2013 ITE score after controlling for the 2012 ITE score.A total of 192 residents participated in the study. We included only 135 participants in the primary analysis because 57 participants did not have both a 2012 and 2013 ITE score. Results from the mixed linear model indicate that the total mean score on the review quizzes was a significant [t(127) = 6.68; ± 1.8 on a 10-point scale. They also felt that these sessions aided in learning (mean 7.7 ± 1.8), assisted in preparation for the ITE (mean 6.7 ± 2.1), and helped identify content areas of weakness (mean 7.6 ± 2.0). Participants were equivalent on whether the ARS review sessions prompted them to study more (mean 5.8 ± 2.7).One hundred forty-six participants (76.0%) completed the survey evaluation of the ARS. Of the 146 residents who completed the attitudinal survey, 95.8% (140) stated “yes” they would like ARS to be used more often in resident education. Participants overall enjoyed the ARS review sessions with a mean score of 8.7 This study found a positive correlation between total mean scores on review quizzes delivered by an ARS and ITE scores, after controlling for prior ITE score. These results suggest that review quiz scores may be predictive of ITE scores. Many programs use various forms of “practice tests” or “quizzes” as preparation, but there is little published data in EM to suggest that performance on these tests or quizzes can predict ITE scores.Residents who have done poorly on the ITE are often encouraged or required to complete some form of remediation or targeted educational intervention; this can improve future outcomes.Consistent with prior research on ARS, participants in our study provided positive feedback about this type of educational intervention. This is also not surprising as an ARS allows for increased interactivity and active learning, which are both enjoyable to learners and can positively impact outcomes.13In addition to being engaging and stimulating, the ARS when used for ITE preparation or core content knowledge acquisition for residents has two additional features that are important specifically for group testing, including anonymity and self-assessment. It is clear based on many reports that students value anonymity;Displaying all responses also allows learners to gauge their performance against the group, a critical feature for ITE preparation. There is some evidence to suggest that students like to know how well they are performing relative to their peers.This information will significantly contribute to the current body of knowledge in that we have found a potential predictor of ITE scores in a method that trainees view positivelyThis study has several limitations. Although there are a large number of participants in our study, the number of questions in each session (10) was small. A greater number of questions/topics would likely more accurately stratify resident knowledge base. RoshReview questions that we used do not have validity evidence. It is unclear if these questions correspond accurately to the ITE material. However, the authors, who are all leaders in EM education, provided content validity in the questions used in the review sessions, although item analysis on the questions was not performed.Three of the study sites did not complete all the scheduled quizzes. There were logistical issues with conference scheduling and technical difficulties that prevented site investigators from completing the ARS quizzes within the designated month. Although this is a real limitation of the study, given that there were six sites, multiple sessions and multiple questions, we don’t believe the analysis or study outcome was compromised.We chose to study the ARS as a potential predictor of ITE scores, but certainly paper quizzes or independent computer quizzes with immediate feedback could similarly correlate with performance. Comparing the various evaluation modalities is certainly an area of future research.Finally, as this study only looked at mean total scores across multiple months and quizzes (12 quizzes over six months), we do not know the minimum number of ARS quiz scores necessary  that are correlated with higher ITE scores. This is an area that requires future research.Performance on review quizzes delivered by an audience response system is correlated with resident in-training exam scores. This type of review is viewed positively by residents and can assist residents in identifying areas of weakness and preparing for the in-training exam.


On the other hand, biomedical application of graphene is a relatively new front with significant potential. Many recent reports have indicated that understanding of graphene-cell  interactions; particularly the cellular uptake mechanisms are still challenging. Therefore, use of graphene or graphene oxide properly embedded in suitable PLA matrices can positively impact and accelerate the growth, differentiation, and proliferation of stem cells, conceivably minimizing concerns over cytotoxicity of graphene. As such, PLA-graphene composites hold great promise in tissue engineering, regenerative medicine, and in other biomedical fields. However, since PLA is classified as a hard bio-polyester prone to hydrolysis, understanding and engineering of thermo-mechanical properties of PLA-graphene composites are very crucial for such cutting-edge applications. Hence, this review aims to present an overview of current advances in the preparation and applications of PLA-graphene composites and their properties with focus on various biomedical uses such as scaffolds, drug delivery, cancer therapy, and biological imaging, together with a brief discussion on the challenges and perspectives for future research in this field.Due to its biodegradable and bioabsorbable characteristics polylactic acid (PLA) has attracted considerable attention for numerous biomedical applications. Moreover, a number of tissue engineering problems for function restoration of impaired tissues have been addressed by using PLA and its copolymers due to their biocompatibility and distinctive mechanical properties. Recent studies on various stereocomplex formation between enantiomeric PLA, poly( The l-isomer is a biological metabolite and constitutes the main fraction of PLA derived from renewable sources since the majority of lactic acid from biological sources exists in this form [l- and d, l-enantiomers, PLA can crystallize in three forms . Thorough understanding of the intrinsic structural, thermal, and physicochemical properties of PLA polymers along with the knowledge of how such properties can be tuned and manipulated with nanomaterials have fueled remarkable biotechnological interest in PLA nanocomposites [Polylactic acid (PLA) polymers are synthesized and obtained from renewable agricultural resources by polymerization of lactide, which is the cyclic di-ester of lactic acid . For allhis form . Dependimposites ,5,6. Themposites  presentsmposites . Althougmposites ,10.co-glycolic acid) (PLGA) occurs by hydrolysis leading to metabolite monomers, lactic acid, and glycolic acid. Because these two monomers are endogenous and easily metabolized by the body via the Krebs cycle, a minimal systemic toxicity is associated with the use of PLGA as biomedical material and drug releasing vehicle [PLA polymers have already been demonstrated as surgical implant materials ,12,13, d vehicle .l-lactic acid interference screws were used for graft fixation during anterior cruciate ligament (ACL) reconstruction, the devices were reported to be mechanically weaker than their metallic counterparts and often fractured during implantation [According to Rasal et al. , PLA polantation . Secondlantation . Howeverantation . Moreoveantation ,27. Thirantation ,29. Noneantation  and blenantation . Stereo-antation .2/g), outstanding mechanical strength  and unparalleled thermal conductivity (~5000 W/m/K). As such, it is a highly popular nanoscale additive for reinforced biopolymers [Graphene, on the other hand, has been at the forefront in biotechnological applications ,34,35,36polymers . Biosafepolymers ,40,41. Ipolymers ,43.Among graphene derivatives, graphene oxide (GO) has been widely explored for in vitro and in vivo drug delivery and imaging, taking advantage of its high solubility and stability in physiological solutions, low cost and scalable production, and facile biological/chemical functionalization ,42,43,44As such, thermo-mechanical properties of PLA polymers are directly related to their biomedical performance when interfaced with biological systems, since these properties can be used to optimize important design criteria such as modulus, strength, morphology, crystallinity, biocompatibility, and, in turn, these properties can affect cell response, tissue regeneration, and in vivo degradation. Moreover, recent research indicates that thermal effects on the crystallinity of not only PLA polymers but also other bio-polyesters is very critical for cell biocompatibility and drug release dynamics . Since, One of the most important performance comparison criteria between biodegradable polymers and conventional oil-based polymers is thermal stability along with moisture retention issues. Although mechanical properties of PLA polymers match those of poly (PET) polyesters, for instance, their thermal stability is not as high as PET polymers . ThermalA comprehensive review by Tan et al.  illustram of homo-chiral crystals (160 °C). They argued that PLLA-rich sb-PLAs can be used as more robust and high-performance resins compared to PLA; minimizing the use of d-lactic acid which is more expensive than l-lactic acid.Hirata and Kimura  conductel-lactide), poly(l/d-lactide) and their blends with poly(d-lactide). The isothermal spherulitic crystal growth rate and its dependence on temperature were measured using tapping mode atomic force microscopy and ex-situ isothermal crystallization. Further, they also investigated the crystallization kinetics of blends of poly(l-lactide) and poly(l/d-lactide) with poly(d-lactide). The typical crystalline structure of PDLA polymer annealed at 100 °C can be seen in the atomic force microscope image in Yuryev et al.  studied l-lactic acid) chain. Thermally annealed specimens retained higher values of tensional and flexural modulus of elasticity, impact strength, and heat resistance. They also showed that while PDLLA and amorphous PLLA presented a heat resistance very near to their glass transition temperature (Tg), annealed PLLA demonstrated a better behavior in the sense that it was more stable at temperatures of 50 °C or higher, due to its crystallinity induced stability.Perego et al.  analyzedIn a highly cited work, Carrasco et al.  processeAs can be seen from this section, crystallization of PLA polymers is a very complex thermal process. Many factors such as post annealing, aging, stereocomplexation, cooling or heating rates, plasticizers not only play a significant role in the crystallization temperature but also in the shape, size, type, and density of the crystals that would nucleate and form, eventually determining the final thermomechanical properties of the polymer.The unique crystalline properties of PLA polymers render them attractive platforms for controlling cellular behavior. In fact, homo-composites of PLA polymers with different crystallinity or engineering PLA polymers with crystallinity gradients have been inspired by the occurrence of natural tissues presenting continuous variations of properties along one direction, such as ligament-to-bone, tendon-to-bone, and dentin-to-enamel interfaces ,58. The Strip-shaped blend films were annealed to allow PLLA to crystallize as shown in 4 cells/mL and kept in culture for periods up to two weeks. They concluded that cell viability was not affected by the different tested conditions. However, cell proliferation was increased in the high molecular weight amorphous samples and cells seemed to have higher adhesion patterns on semi-crystalline samples. They attributed these observations to different rates of integrin interaction with the substrate leading to different patterns of focal adhesion point formation. Sladago et al.  reportedLi et al.  used PLLThey used microscopy and image analysis to ascertain that the MC3T3-E1 cells spread out in a random fashion on the amorphous PLA. At 24 h post-seeding, MC3T3-E1 cells on both types of spherulite surfaces were elongated and aligned along the spherulite radius direction. For the banded spherulite surface with radial stripes and coupling annular grooves, the cell orientation and cell nuclear localization were related to the groove structure. With increasing time, this orientation preference was weaker. They further demonstrated that the patterning of the polymer crystallization structure provides important indicators for guiding cells to exhibit characteristic orientation and morphology especially in the early stages of regeneration.Using a novel high-throughput method for creating gradients in polymer crystallinity, Washburn et al.  demonstrPLA polymer-graphene nanocomposites have been increasingly gaining in popularity due to attractive features offered by both materials ,63. NoraWu et al.  conducteWang et al.  preparedc) was increased in samples due to better dispersion and grafting reaction between GnPs and PLA. Isothermal tests also showed that commencement of the crystallization time was affected by the functionalization and then decreased. They also concluded that the growth mechanism of crystallization did not change significantly.Manafi et al.  preparedc) studied by Zhao [The effects of GO with polar groups and functionalized graphene oxide (fGO) with non-polar groups on the isothermal crystallization of PLLA were studied by Zhao et al. . Functio by Zhao .Sun and He  preparedc of 135 °C. They observed a diffuse scattering ring in the first pattern (t = 0 min) for all the samples, indicating no crystals could have survived in the melt. With increasing crystallization time, the isotropic lattice planes, i.e., (200)/(110) reflection, can be observed and gradually sharpen until the completion of crystallization, correlating with the formation and growth of the PLA crystals. In contrast to neat PLA, the advent of ultrasonically treated rGO shortens the appearance time of the diffraction peak remarkably , demonstrating the superb nucleation ability of rGO.Liang et al.  studied Their main conclusion was that both rGOw and rGOp could serve as heterogeneous nucleation agents for PLA, decreasing the induction period of crystallization and accelerating the overall crystallization rate. Prolonged ultrasound time, however, gradually enhanced the nucleation ability of rGOw but suppressed that of RGOp.Xu et al.  fabricatReview of the literature on PLA-graphene nanocomposites in the form of free standing films produced either by solvent processing or by melt molding/extrusion indicates that there is still a significant lack of established recipe or nanocomposite fabrication protocol that could be used to enhance the elastic modulus or elongation at break values of PLA polymers using graphene-based materials. This is due to the fact that graphene comes as filler in the form of many stacked layers , which is influenced by the synthesis history. Different lateral size and thickness distribution exist in all these “commercially available” graphene products. Separately, graphene oxide or reduced graphene oxide introduces other parameters such as surface reactive sites and polarity effects. However, most recent reports highlight the necessity to functionalize graphene surfaces or use graphene oxide with graft chemistry  in orderCataldi et al.  fabricatIn the case of PLA, however, both large multi- and few-layer GnPs caused up to 35% increase in elastic (Young’s) modulus compared to other model 2D or 3D fillers; see Cao et al.  producedThey reported that even for such a small percentage of GNS the reinforcing effect is rather significant: In other words, 0.2 wt% GNS incorporation leads to a 26% increase in tensile strength and a 18% raise in Young’s modulus. In their work , Young’sMarques et al.  reportedθ of 17° and 19° corresponding to a typical PLLA pseudo-orthorhombic α structure. These peaks are also present in the XRD pattern of the nanocomposites  at 30 °C increased from 2.2 GPa to 4.1 GPa with the addition of 20 wt% GO-g-PDLA (containing 1 wt% GO). The large mechanical enhancement was ascribed to the reinforcement of GO on the PLLA–PDLA stereocomplex networks. Similarly, this effect is more significant at 195 °C, particularly after 10 wt% PDLA inclusion. They argued that existence of GO can be regarded as the landscape of the ordering of SC helices surrounding the PLA/GO interface. At last, the stereocomplex crystallite, SC, could begin to grow from the GO surface with the hydrogen bonding inter-chain interactions between PLLA and PDLA and finally an SC network would form with the link of PLA chains and enhancement of GO as schematically shown in Xu et al.  demonstrIn biomedicine, polymeric muscle or bone scaffolds must have an appropriate porosity range with an interconnected and open porosity, and have a biodegradable rate and mechanical properties that match the injured tissue. PLA polymers have been extensively studied for this purpose . As expeε-caprolactone (PCL) copolymer, designated as PLC. Exceptional wettability of PLC on graphene foam resulted in PLC forming a thin uniform coating over the graphene foam. This effective wettability allowed the PLC to fill voids and defects that had been present in the graphene foam. The healing of defects in conjunction with the formation of PLC bridges caused enhanced strength and ductility in the GrF-PLC scaffold. They conducted nano-indentation and macroscale tensile tests and demonstrated that significant increase in strength in both compression and tension at multiple scales occurred, as shown in Nieto et al.  demonstrChen et al.  producedThermal stability was also shown to be improved, with 90 °C increase in degradation temperature as well as the new formation of better crystalline structures. They also conducted cell culturing experiments and results revealed excellent cell viability e–h of 3DChen et al.  further Staphylococcus aureus and the Gram-negative Escherichia coli. They attributed this to the inherent antibacterial property of GO sheets with high specific surface area  (PLGA) embedded with GO nanosheets by electrospinning, and investigated their physiochemical properties including morphological, surface-chemical, mechanical, and thermomechanical properties. They showed a 2-fold increase in tensile modulus as compared to that of pristine PLGA nanofibers. Storage modulus and glass transition temperatures of the PLGA/GO (2 wt%) nanocomposites were much higher than those of PLGA nanofibers and PLGA/GO (1 wt%) nanocomposite nanofibers, as shown in Yoon et al.  construcInterestingly they claimed that the incorporation of GO nanosheets according to concentration led to effective enhancement of their mechanical and thermomechanical properties compared to those of pristine PLGA nanofibers. This enhancement was attributed to stronger interfacial interactions caused by stronger chemical bonding between the PLGA and GO nanosheets and the axial alignment of the GO nanosheets embedded nanocomposite nanofibers. They also showed that nanocomposite nanofibers were more hydrophilic than PLGA nanofibers. In order to investigate the effects of GO nanosheets on nanocomposite biocompatibility, PC 12 neuronal cells were cultured for two days on various nanofibrous scaffolds, and the proliferation and viability of the cells were measured. Biocompatibility tests c–f showeg-PEG were incorporated in PLA polymer as reinforcing fillers to fabricate nanofibrous scaffolds of PLA, PLA/GO, and PLA/GO-g-PEG, which were prepared by means of electrospinning. They measured decreases in complex viscosity for PLA/GO-g-PEG electrospinning suspensions and attributed these observations to the plasticizing effect of the grafted PEG molecules on the surface of GO.Zhang et al.  surface g-PEG had a greater influence than GO in improving the thermal stability of PLA. Tensile tests showed that the addition of GO and GO-g-PEG in PLA achieved significantly improved tensile stress, as shown in g-PEG was more effective in reinforcing PLA than GO due to the grafted PEG chains, which improved the filler dispersion as well as the adhesion between GO and PLA. Moreover, PLA/GO and PLA/GO-g-PEG composite nanofibrous scaffolds were found to be non-toxic to NIH 3T3 cells and were capable of supporting cell attachment and growth  and Gram negative bacteria Escherichia coli (E. coli) as well. Although promising results were reported by Pal et al. [Pal et al.  formulatl et al. , furtherLuo et al.  fabricat2 as blowing agent. PLA/GO nanocomposite foams with oriented and highly elongated cell structure were prepared for the first time in this study. They prepared the nanocomposites by a solution mixing method at various GO contents. The thermal and rheological properties, and CO2 absorption ability of the composites, were investigated and compared with neat PLA. It was found that the incorporation of GO improved the crystallinity of the PLA matrix. The addition of GO enhanced the storage modulus, loss modulus, and complex viscosity of the PLA matrix as well, and the improvements increased with increase of GO content. The unidirectional microcellular foaming revealed that the PLA/GO nanocomposites had the ability to form highly elongated cell structure. Compared to neat PLA, the relatively high GO content  in PLA/GO nanocomposites showed significantly higher expansion ratio, average foam cell size, and cell diameter ratio in the long axis and minor axis. These behaviors were caused by the enhanced CO2 absorption rate, PLA/GO matrix viscosity, and the unidirectional foaming process. They did not demonstrate biocompatibility or discuss any potential biomedical applications although their cellular architectures were claimed to be very suitable as 3D biomedical scaffolds.Kuang et al.  investigAlthough PLA polymer is regarded as one of the most suitable biopolymers for biomedical applications with many successful in vitro and in vivo demonstrations to date, it is now understood that homo-composites of PLA polymers are not only thermally and mechanically superior to pure PLA but also perform better as drug release platforms . In otheOn the other hand, clearly, graphene has the ability to modulate crystallinity and the final thermomechanical properties of PLA polymers including SCs. However, the effectiveness lies in the proper surface functionalization of graphene of GO, a priori. As such, compatibilization of graphene or graphene derivatives with PLA SCs can yet produce significant improvements in the thermomechnical properties of SCs . To achiAn outstanding biomedical issue that still needs to be addressed is the fact that various chemical pathways and agents used or proposed for surface functionalization or grafting graphene or graphene oxide nanosheets so that they can be inserted into PLA matrices must not yield cytotoxicity. Furthermore, their fate after passing through the cell membranes should be carefully evaluated. This issue is still open; however, encouraging new results are being published ,96. SimiSo far many published works on PLA/graphene composites exclusively focus either on the thermomechanical properties or on cell compatibility and behavior. Hence, none of them can be explicitly singled out as an ideal candidate for clinical applications. In fact, both properties are interrelated as was shown by some recent studies on the effect of PLA crystallinity on cell proliferation. Therefore, it is suggested that future studies on PLA-graphene systems should focus on surface functionalization of graphene and graphene oxide with biomacromolecules and incorporation of these modified graphene nanoflakes into PLA polymers, particularly into PLA stereocomplexes. The characterization should clearly demonstrate changes in crystallinity, thermomechanical properties due to functionalized graphene addition, and how this translates into cell proliferation and cytocompatibility compared to simple PLA polymer/graphene systems.Since PLA polymers can be processed with ease in many different ways such as solution, spinning, extrusion, and injection, they offer unique possibilities to produce graphene–PLA nanocomposites with higher-order 3D architectures such as sponge-like macroporous scaffolds, nanofiber mats or hollow micrometer-sized spheres, which are ideal platforms for surgical reconstruction and drug delivery . AlthougThe future seems to be the combination of PLA stereocomplexes with graphene and GO rather than PLA as PLA stereocomplexes are not only thermomechanically superior but also more flexible in terms of interfacial engineering, opening up many promising additional applications in delivery of drugs, genes, proteins, growth factors, and other biomolecules for cancer and other disease therapies. As seen, advances in PLA/graphene material systems are growing rapidly and this trend, the author believes, will continue and even speed up in the years to come.


IntroductionEmergency departments (EDs) see a surge of intoxicated patients during large public summer events. These patients can be distracting and complicated for ED staff to care for.MethodsWe developed two cases to prepare emergency department staff for an anticipated surge of patients related to a large music festival that occurs proximal to our pediatric hospital. We developed and performed cases of simulated patients with alcohol intoxication and methylenedioxymethamphetamine (MDMA) ingestion to review medical management of these patients, as well as to review many of the social aspects of the cases. We surveyed simulation (sim) session participants to assess the degree to which the sessions were helpful and to glean ideas on how to improve sessions for future use.ResultsOver the course of two years, we have hosted eight simulations, for a total of 57 participants comprising various healthcare roles. We achieved an 85% response rate in the post-simulation surveys. The sessions were overall well-received and left participants feeling better prepared to care for intoxicated patients.DiscussionDespite having a large number of staff from many disciplines working varied schedules, we were able to provide simulation training to many of them in preparation for an expected surge of intoxicated patients. Participants appreciated the training and gave feedback to improve sessions in the future. Emergency departments (EDs) see a surge of intoxicated adolescent patients during summer festivals, concerts, and other large public events. Our hospital, located in downtown Chicago, sees a particularly large increase in patient volume during the weekend coinciding with the annual Lollapalooza music festival. Lollapalooza, which began as a small concert series 25 years ago, has turned into an enormous local attraction. In 2016, there were an estimated 400,000 people in attendance, and approximately 20,000 of them were adolescents. Aggregate data from Chicago’s children’s hospitals indicate that in 2014 over 100 children were seen in pediatric EDs with Lollapalooza-related complaints; this number decreased to 88 in 2015 . In anotThe surge of intoxicated teenagers that presents to the ED from Lollapalooza each summer is disruptive to the usual patient flow in the ED and requires additional staffing, including increased physicians, nurses, social workers, and environmental staff. Although there are several studies examining ED preparations for large events , most of this data focuses on how the event itself will communicate with local hospitals to coordinate care of attendees in need -8. ThereOur target audience was all clinical providers in the ED, at all training levels. We reached medical students, residents, attending physicians, nurses, and paramedics. In our ED, the purpose of these simulation sessions was specifically to prepare for a known influx of complicated intoxicated patients. These same sessions could be used in any other ED, either to prepare for a predicted surge of intoxicated patients or simply to review these interesting and dangerous toxidromes at any time of the year.We developed two cases to simulate patients with alcohol intoxication and methylenedioxymethamphetamine  (MDMA) ingestion. These agents were chosen for two different reasons. Alcohol was chosen because it is the most ubiquitous recreational substance seen in intoxicated patients coming from Lollapalooza. While most providers have experience treating alcohol intoxication, we wanted to highlight some of the unique issues associated with the concert during this case, including that many teenagers carry fake identification cards to the event and can therefore be difficult to identify, as well as the possibility of having other substances “slipped into their drink”, as they are often obtaining alcohol from other concert-goers and not from legal vendors. MDMA was chosen because, although it is seen less commonly, its clinical presentation is somewhat unusual and its clinical consequences tend to be much more severe. In addition, MDMA toxicity can involve hyperthermia, which can be a complication from the usual weather during the August concert, and this allows us to discuss cooling measures due to any cause. The simulation sessions and the subsequent debriefing sessions were tailored over time to address gaps in knowledge as well as preferences and suggestions of participants.The two simulation cases were developed based on the learning objectives outlined above. The cases are outlined in Tables Equipment and environmentSimulation sessions took place in the ED, specifically in the resuscitation bays. This location was chosen because of its proximity to the learners during their typical work day and because it is nearly identical to the rooms that are used for actual patient care. This allowed the sessions to appear very realistic relative to real patient care. The equipment required included monitors, intravenous (IV) insertion equipment, and other items that are commonly found in a resuscitation bay. We did not use a manikin for our simulations, but rather used a standardized patient (SP) who was dressed to appear to be a concert-goer.PersonnelAs mentioned above, we used an SP in lieu of a simulator for these sessions. We felt that this would provide the most realistic experience for the team working through the case. The SP each summer has been an intern with the simulation program and is a high school or college student. The SP dressed as a festival-goer and practiced being intoxicated and agitated with the simulation team prior to the actual sessions. Another person (either a staff member or a second intern) acted as the older sibling for the alcohol ingestion case to provide a more realistic social environment for the simulation. There were two to three facilitators leading the case, including one person designated to run the simulated monitors. Everyone else involved were learners.Sessions were scheduled during the two weeks prior to the festival. We knew it would be challenging to recruit participants at times that worked well for everyone. The nature of the ED shift schedule does not allow for a single time of day that will accommodate everyone. Therefore, we conducted multiple sessions at different times of day (including very early mornings and very late nights) over the course of two weeks in an effort to maximize participation, especially for night-shift nurses. Sessions were targeted toward staff who would be working during the weekend of the festival. Staff  actively working a shift were invited to participate and were notified at the start of their shift that the simulation would be occurring. The leaders in charge of staffing tried to coordinate assignments in order to allow staff who would be present during the festival to attend the simulations, while those who were not working the festival weekend continued with usual patient care in the ED. In addition, physicians who were scheduled to work during the festival weekend were invited via email to attend a session outside of their scheduled shift times. Medical students working in the ED and in the urgent care center were invited to participate as observers. In order to quantify the quality and effect of the simulation sessions, we administered a survey after the simulations sessions to all participants .AssessmentFollowing the simulation sessions, participants were offered the opportunity to evaluate the session using a standardized survey Table . The surDebriefingAt the conclusion of the cases, a debriefing session was held with all of the learners and the two to three leaders of the session. We discussed general topics such as how everyone felt about the session, what questions came up, and how the group seemed to interact in terms of communication and teamwork. We also provided learners with a handout of tips and learning points related to the music festival, ingestions of common substances seen at events like this, and basic management strategies. This handout Table  was alsoIn total over two years, we hosted eight simulation sessions, comprising 16 case scenarios (two cases per session). We had 33 participants in the first year and 24 participants in the second year. The groups comprised approximately two-thirds nurses and paramedics and one-third residents and attendings. There were also several medical students who attended, participating only as observers.We achieved an 85% response rate from participants on the survey . Overall, the sessions seemed to be very well-received, and learners were excited to participate. Of all participants in the simulation sessions, 80% reported that they had at least one year of experience taking care of intoxicated patients from the summer music festival. We asked participants to rank statements on a Likert scale of 1 to 5 . The results from this section of the survey are shown in Table Additionally, we asked participants for specific suggestions for improvements. While many responded that they did not have any ideas for improvements, several suggestions were made, and these were incorporated into the sessions during our second year of this program. Some examples of suggestions are shown in Table The initial design of the simulation sessions was based almost entirely on addressing medical management of patients with acute alcohol intoxication. There was little focus on the social aspects of care or the pathophysiologic mechanisms of possible ingested substances and the reasons for various management strategies. While we felt that our simulation sessions had helped prepare providers for the medical needs of the patients, we knew that there were more dimensions to patient care that could be better addressed in future sessions. Based on the suggestions from the pilot year, we made changes and additions to the second year’s simulations. Representatives from our social work department helped to develop a pathway for how to identify patients who were not carrying any formal form of identification . We also made the “tip sheet” more robust to review more pathophysiology. We spent a longer time during debriefing sessions reviewing the reasoning for various medical interventions and discussing possible complications of intoxications that may not have come up during the scenario itself.The results of our simulation sessions, in the form of subjective assessments by the participants of the perceived benefit of the sessions, was overall quite positive. The sessions addressed the major issues that our ED faces during the Lollapalooza weekend, i.e. an influx of unusually intoxicated patients. While it is impossible to objectively quantify the impact of the simulation sessions on individual patient care experience, we have found that, subjectively, participants seem quite satisfied with their experience. As noted above, participants report that they feel more prepared to take care of intoxicated patients after taking part in the simulation sessions.A benefit of the sessions that we did not initially anticipate but have noticed upon reflection is that the simulation sessions serve as a form of a team-building experience in the days leading up to the festival weekend. We specifically enlist providers who are scheduled to work during the festival to participate in the simulation sessions. This allows learners to focus on material that is relevant to their upcoming shifts in the ED and provides an opportunity for providers to practice being on a team together. Teammates build camaraderie and trust, so that when the patient surge arrives, everyone feels like they are working on a team that can communicate effectively.Challenges/barriersPreparing for a festival weekend using simulation sessions has its fair share of challenges. Running simulation sessions in a busy ED and trying to coordinate the timing of sessions with the providers who need the training the most is difficult. We are fortunate to have many providers who are willing to stay late or arrive early in order to participate in this valuable learning experience. Scheduling time and space will continue to be a barrier and could be a challenge to implement the session in other locations where there isn’t robust support for simulation education. Finalizing and announcing the schedule well in advance of the planned sessions has been helpful in circumventing this challenge.Another challenge common to all simulation education is the realistic quality of the patient and the flow of the session. We have invested a great deal of effort to make our festival preparation simulation sessions as high-fidelity as possible. Using an SP instead of a manikin, as well as a live confederate to act as a friend or family member, is a great step toward making these sessions realistic. We’ve been fortunate to have great enthusiasm from our interns who have played the part of the drunk teenager. Not all hospitals or departments will have the same fortune of having such enthusiastic and available SPs.Future changes/revisionsWe plan to continue running the festival-preparations annually, as they have been very well-received, helpful, and fun. The basic content of these cases  will remain the same, but we will continue to incorporate suggestions from participants in order to tailor the education sessions to the needs of the learners. We plan to re-administer the survey each year with the questions altered slightly and space asking for more specific feedback.In preparation for a known surge of intoxicated teenagers related to a summer music festival, we developed and carried out two simulation sessions for use with a multidisciplinary team within the pediatric ED. Despite having a large number of staff from many disciplines working varied schedules, we were able to provide helpful simulation training to many participants. Participants appreciated the training and gave feedback to improve sessions for the future. These simulation cases could be used in a wide variety of other ED settings, either in preparation for a predicted surge of intoxicated patients or simply to review these interesting and dangerous toxidromes at any time of year.