Risk Factors for Postdischarge Major Thromboembolism and Mortality in Hospitalized Patients with COVID-19 with Cardiovascular Comorbidities: Insights from the CORE-19 Registry.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with venous and arterial thromboembolism (VTE and ATE) and all-cause mortality (ACM) in hospitalized patients. High-quality data are needed on postdischarge outcomes in patients with cardiovascular disease. OBJECTIVES: To analyze outcomes and identify risk factors for ATE, VTE, and ACM in a high-risk subgroup of hospitalized COVID-19 patients with baseline cardiovascular disease. METHODS: We investigated postdischarge rates and associated risk factors of ATE, VTE, and ACM in 608 hospitalized COVID-19 patients with coronary artery disease, carotid artery stenosis (CAS), peripheral arterial disease (PAD), or ischemic stroke. RESULTS: Through 90 days postdischarge, outcome rates were: ATE 27.3% (10.2% myocardial infarction, 10.1% ischemic stroke, 13.2% systemic embolism, 12.7% major adverse limb event); VTE 6.9% (4.1% deep vein thrombosis, 3.6% pulmonary embolism); composite of ATE, VTE, or ACM 35.2% (214/608). Multivariate analysis showed significant association between this composite endpoint and age >75 years (odds ratio [OR]: 1.90, 95% confidence interval [CI]: 1.22-2.94, p = 0.004), PAD (OR: 3.23, 95% CI: 1.80-5.81, p ≤ 0.0001), CAS (OR: 1.74, 95% CI: 1.11-2.75, p = 0.017), congestive heart failure (CHF) (OR: 1.84, 95% CI: 1.02-3.35, p = 0.044), previous VTE (OR: 3.08, 95% CI: 1.75-5.42, p < 0.0001), and intensive care unit (ICU) admission (OR: 2.93, 95% CI: 1.81-4.75, p < 0.0001). CONCLUSION: COVID-19 inpatients with cardiovascular disease experience high rates of ATE, VTE, or ACM through 90 days postdischarge. Age >75 years, PAD, CAS, CHF, previous VTE, and ICU admission are independent risk factors.

Postdischarge thromboembolic outcomes and mortality of hospitalized patients with COVID-19: the CORE-19 registry.

Thromboembolic events, including venous thromboembolism (VTE) and arterial thromboembolism (ATE), and mortality from subclinical thrombotic events occur frequently in coronavirus disease 2019 (COVID-19) inpatients. Whether the risk extends postdischarge has been controversial. Our prospective registry included consecutive patients with COVID-19 hospitalized within our multihospital system from 1 March to 31 May 2020. We captured demographics, comorbidities, laboratory parameters, medications, postdischarge thromboprophylaxis, and 90-day outcomes. Data from electronic health records, health informatics exchange, radiology database, and telephonic follow-up were merged. Primary outcome was a composite of adjudicated VTE, ATE, and all-cause mortality (ACM). Principal safety outcome was major bleeding (MB). Among 4906 patients (53.7% male), mean age was 61.7 years. Comorbidities included hypertension (38.6%), diabetes (25.1%), obesity (18.9%), and cancer history (13.1%). Postdischarge thromboprophylaxis was prescribed in 13.2%. VTE rate was 1.55%; ATE, 1.71%; ΑCM, 4.83%; and MB, 1.73%. Composite primary outcome rate was 7.13% and significantly associated with advanced age (odds ratio [OR], 3.66; 95% CI, 2.84-4.71), prior VTE (OR, 2.99; 95% CI, 2.00-4.47), intensive care unit (ICU) stay (OR, 2.22; 95% CI, 1.78-2.93), chronic kidney disease (CKD; OR, 2.10; 95% CI, 1.47-3.0), peripheral arterial disease (OR, 2.04; 95% CI, 1.10-3.80), carotid occlusive disease (OR, 2.02; 95% CI, 1.30-3.14), IMPROVE-DD VTE score ≥4 (OR, 1.51; 95% CI, 1.06-2.14), and coronary artery disease (OR, 1.50; 95% CI, 1.04-2.17). Postdischarge anticoagulation was significantly associated with reduction in primary outcome (OR, 0.54; 95% CI, 0.47-0.81). Postdischarge VTE, ATE, and ACM occurred frequently after COVID-19 hospitalization. Advanced age, cardiovascular risk factors, CKD, IMPROVE-DD VTE score ≥4, and ICU stay increased risk. Postdischarge anticoagulation reduced risk by 46%.

Endobronchial Foreign Body Presenting as Exacerbation of Asthma.

Airway foreign bodies are a leading cause of death among children and require urgent recognition by medical personnel. While most cases are diagnosed readily from a clinical history of acute respiratory distress, some cases remain more indolent and present later. We report the case of a 7-year-old boy who aspirated a "LEGO" toy and presented with a week history of increasing respiratory distress compatible with known asthma. Despite a normal chest X-ray, a low-dose computed tomography showed the presence of a foreign body in the left main bronchus, which was subsequently removed by fiberoptic bronchoscopy. Our case serves to reemphasize the importance of considering airway foreign bodies as a cause of respiratory distress, especially in young children.

Basic nutrition knowledge of recent medical graduates entering a pediatric residency program.

OBJECTIVE: This study assesses the basic nutritional knowledge of fourth year medical/osteopathic school graduates entering a pediatric residency program and compares the knowledge of the medical students to that of the patients and parents who completed the same survey previously. METHODS: Medical and osteopathic school graduates entering a pediatric residency program completed an 18-question nutrition survey during resident orientation in June of 2011 and 2012. RESULTS: The incoming interns averaged answering 52% of the questions correctly. Interns did better than both groups but the only statistically significant difference was between the interns and the non-eating disorder adolescents and their parents (p<0.001). CONCLUSION: Incoming residents to a pediatric residency program appear to be deficient in basic nutritional knowledge. With the ever increasing burden of obesity and its associated co-morbidities on society, it is imperative that medical education focuses on preparing physicians to appropriately counsel all populations on proper nutrition.

Thyroglobulin flare response after radioiodine ablation in 2 patients with differentiated thyroid cancer.

Serum thyroglobulin (Tg) measurement facilitates monitoring differentiated thyroid cancer. We describe 2 patients with papillary thyroid cancer who developed dramatic transient serum Tg level elevations within 1 week of I radioiodine (RAI) ablation without cancer recurrence on follow-up. The first patient received recombinant human thyroid-stimulating hormone injections. The pre-injection Tg level was 3.8 µg/L and increased to 3060 µg/L 3 days post-RAI. In the second patient, the serum Tg level increased from 1.3 µg/L to 209.9 µg/L 7 days after RAI. This transient early serum Tg "flare response" could be misleading if interpreted as suggesting more extensive high-risk thyroid cancer.

An assessment of basic nutrition knowledge of adolescents with eating disorders and their parents.

UNLABELLED: Objective: This study aims to determine and compare the level of basic nutrition knowledge of adolescents with eating disorders and their parents to adolescents without eating disorders and their parents. MATERIALS AND METHODS: This six-month convenience based survey recruited a total of 182 adolescents with and without an eating disorder and their parents. The surveys were conducted in a suburban adolescent medicine office. Main outcome measures were based on the 18 basic nutrition questions, while means, standard deviations, Wilcoxon Rank Sum Test, and χ2 were all employed for the analysis. RESULTS: None of the groups correctly answered more than half of the questions. In terms of the percentage of correct responses, there was a statistically significant difference between adolescents with eating disorders and their parents compared with adolescents without an eating disorder and their parents. Fewer than 16% of respondents in each group correctly answered the recommended daily caloric balance of fats, carbohydrates, and proteins. CONCLUSIONS: There is a deficiency in basic nutrition knowledge among adolescents with and without eating disorders and their parents. A significant increase in basic nutrition education needs to occur in order to increase the understanding of what is a "healthy" diet.

Urinary Iodine Clearance following Iodinated Contrast Administration: A Comparison of Euthyroid and Postthyroidectomy Subjects.

Purpose. To compare iodine clearance following iodinated contrast administration in thyroidectomised thyroid cancer patients and euthyroid individuals. Methods. A convenience population (6 thyroidectomised thyroid cancer patients and 7 euthyroid controls) was drawn from patients referred for iodinated contrast-enhanced computed tomography (CT) studies. Subjects had sequential urine samples collected up to 6 months (50 samples from the thyroidectomised and 63 samples from the euthyroid groups). t-tests and generalised estimating equations (GEE) were used to test for group differences in urinary iodine creatinine ratios. Results. Groups had similar urinary iodine creatinine ratios at baseline, with a large increase 2 weeks following iodinated contrast (P = 0.005). Both groups had a return of urinary iodine creatinine ratios to baseline by 4 weeks, with no significant group differences overall or at any time point. Conclusions. Thyroidectomised patients did not have a significantly different urinary iodine clearance than euthyroid individuals following administration of iodinated contrast. Both had a return of urinary iodine creatinine ratios to baseline within 4 weeks.

Multimodality imaging of aortic dimensions: comparison of transthoracic echocardiography with multidetector row computed tomography.

BACKGROUND: With recent advances in multimodality cardiac imaging, a number of methods exist for the noninvasive assessment of aortic disease. Although multidetector row computed tomography (MDCT) remains the gold standard for aortic measurements, there are a number of limitations including radiation and contrast-induced nephropathy. Transthoracic echocardiography (TTE) is an alternative to MDCT for providing accurate anatomic assessment of aortic root and ascending aorta dimensions. OBJECTIVES AND METHODS: To determine the accuracy of two-dimensional (2D) TTE for determining aortic measurements in comparison to MDCT, a retrospective study of individuals with varying aortic root and ascending aorta dimensions was performed. RESULTS: There were 116 patients (77 males, mean age 49 ± 12 years) in total. The maximum aortic diameters by 2D TTE were 26.1 ± 4.3 mm (annulus), 32.4 ± 5.6 mm (sinuses), 30.1 ± 5.9 mm (sinotubular [ST] junction), and 33.4 ± 7.3 mm (ascending aorta). The maximum aortic diameters by MDCT were 30.1 ± 4.1 mm (annulus), 35.8 ± 5.8 mm (sinuses), 33.2 ± 5.9 mm (ST junction), and 37.4 ± 7.6 mm (ascending aorta). There was good to excellent correlation between 2D TTE and MDCT at all four levels of the aorta (annulus: r = 0.84; sinuses: r = 0.93; ST junction: r = 0.93; ascending aorta: r = 0.88). There was a consistent underestimation of aortic measurements obtained by 2D TTE when compared to MDCT. CONCLUSION: 2DTTE is a feasible, accurate, and reproducible method for the noninvasive assessment of thoracic aortic diameters as compared to MDCT.

Dysmetabolic Signals in "Metabolically Healthy" Obesity.

BACKGROUND: Obesity is associated with decreased insulin sensitivity, atherogenic dyslipidemia and hypertension, but clinical studies have also identified a "metabolically healthy" obese phenotype. OBJECTIVE: To compare the characteristics of so-called "metabolically healthy" obese (MHO), normal weight subjects (MHNW) and obese with insulin resistance in a nationally representative sample in the United States. DESIGN, SETTING AND PARTICIPANTS: Insulin resistance was defined by a homeostatic model assessment (HOMA) value in the upper tertile for the entire NHANES cohort. "Metabolic health" was defined as the absence of diabetes, insulin resistance, metabolic syndrome, and lipid-lowering therapy. The study evaluated the 314 MHO, 1173 MHNW and 843 insulin-resistant obese from among the 6485 non-diabetic, nno-pregnant adults aged 20-79 years, who participated to the United States National Health and Nutrition Examination Survey, 1999-2004. MAIN OUTCOME MEASURES: Demographic, metabolic, nutrition and physical activity features. RESULTS: MHO and MHNW groups were similar regarding age, and fasting glucose and triglyceride levels. MHO had higher insulin (P<0.0001), insulin resistance as measured with the homeostatic model (p<0.0001), non-HDL cholesterol (P=0.002 in females and P=0.049 in males) and C-reactive protein levels (P<0.0001 in females and P=0.038 in males), and lower high-density lipoprotein cholesterol (HDL) levels (P<0.002). In addition, MHO females had higher low-density lipoprotein (LDL) cholesterol levels (P=0.012) and systolic blood pressure (P=0.02), and lower intake of dietary fiber (P=0.0009) and levels of physical activity (p=0.002). Triglycerides levels were normal in the MHO group. CONCLUSIONS: "Metabolically healthy" obese people have multiple dysmetabolic changes that may signal increased risk for coronary artery disease.

Effect of gender on prehospital refusal of medical aid.

BACKGROUND: "Refusal of medical aid" (RMA) is the term commonly used by emergency medical technicians (EMTs) when someone calls 911 for care (usually the patient or a family member) but, after the initial encounter with the EMTs, the patient refuses emergency medical services transport to the hospital. Some intervention may have been performed, such as taking vital signs or an electrocardiogram, before the RMA. Although there have been multiple studies of the characteristics and outcomes of patients who RMA, little analysis has been done of the role of EMTs in these cases. OBJECTIVE: To analyze the association between EMT gender and the patient's decision to refuse medical aid in the prehospital setting. METHODS: The study was performed using data from one hospital-based ambulance service in an urban setting that participates in the 911 system. This was a case control study that examined the data from consecutive patients who refused medical aid for a 1-year period compared to a control group of non-RMA patients. RESULTS: There was a significantly higher representation of all-male EMT teams in the RMA group (p<0.0001). Using propensity score-matching methodology to control for other factors, all-male EMT teams were 4.75 times more likely to generate an RMA as compared to all-female and mixed-gender EMT teams (95% confidence interval 1.63-13.96, p=0.0046). CONCLUSION: We found that the gender of the EMTs was one of the most important factors associated with RMA, with a much higher frequency of RMAs occurring when both members of the team were male.

Dysmetabolic signals in "metabolically healthy" obesity.

BACKGROUND: Obesity is associated with decreased insulin sensitivity, atherogenic dyslipidemia and hypertension, but clinical studies have also identified a "metabolically healthy" obese phenotype. OBJECTIVE: To compare the characteristics of so-called "metabolically healthy" obese (MHO), normal weight subjects (MHNW) and obese with insulin resistance in the United States National Health and Nutrition Examination Survey, 1999-2004 (NHANES). DESIGN, SETTING AND PARTICIPANTS: Insulin resistance was defined by a homeostatic model assessment (HOMA) value in the upper tertile for the entire NHANES cohort. "Metabolic health" was defined as the absence of diabetes, insulin resistance, metabolic syndrome, and lipid-lowering therapy. The study evaluated the 314 MHO, 1173 MHNW and 843 insulin-resistant obese from among the 6485 non-diabetic, non-pregnant adults aged 20-79 years. MAIN OUTCOME MEASURES: Demographic, metabolic, nutrition and physical activity features. RESULTS: MHO and MHNW groups were similar regarding age, and fasting glucose and triglyceride levels. MHO had higher insulin (P < 0.0001), insulin resistance as measured with the homeostatic model (P < 0.0001), non-HDL cholesterol (P = 0.002 in females and P = 0.049 in males) and C-reactive protein levels (P < 0.0001 in females and P = 0.038 in males), and lower high-density lipoprotein cholesterol (HDL) levels (P < 0.002). In addition, MHO females had higher low-density lipoprotein (LDL) cholesterol levels (P = 0.012) and systolic blood pressure (P = 0.02), and lower intake of dietary fiber (P = 0.0009) and levels of physical activity (P = 0.002). Triglycerides levels were normal in the MHO group. CONCLUSIONS: "Metabolically healthy" obese people have multiple dysmetabolic changes that may signal increased risk for coronary artery disease.

Predictors of insulin resistance in the obese with metabolic syndrome.

BACKGROUND: In the obese, the metabolic syndrome (MetS) is assumed to reflect insulin resistance. OBJECTIVE: To determine the predictors of insulin resistance in obese subjects with MetS. DESIGN: We used the 90th percentile of the homeostasis model assessment (HOMA) to define insulin resistance in 4958 nondiabetic adults evaluated in the National Health and Nutrition Examination Surveys, 1999-2004, and compared the 373 obese subjects who were insulin-resistant (HOMA 9.52+/-5.73) to a control group of 373 obese who had the highest sensitivity to insulin (HOMA 1.79+/-0.44). MEASUREMENTS: MetS was present in 312 (83.6%) obese with insulin resistance and in 156 (41.8%) obese from the insulin-sensitive control group. Demographic, metabolic, and lifestyle variables were analyzed with logistic regression. RESULTS: In a logistic model of insulin resistance given the presence of MetS, the significant predictors were triglycerides (P=0.0021), body mass index (P=0.0096), HDL-cholesterol (P=0.0098), age (P=0.0242) and smoking (P=0.0366). LIMITATIONS: Cross-sectional design prevents elucidation of causality for the association between insulin resistance and MetS. CONCLUSIONS: Insulin resistance is not an obligatory correlate of MetS in the obese. Its likelihood can be predicted by cigarette smoking and by the severity of obesity and dyslipidemia.

Design, implementation, and outcome of a hands-on arthrocentesis workshop.

INTRODUCTION: During a 4-week rheumatology elective at our institution, opportunities for internal medicine residents to perform arthrocentesis were limited, particularly for sites other than the knee. Consequently, residents were inadequately prepared and had less self-confidence to perform such procedures. To overcome these educational deficiencies, an arthrocentesis workshop was developed. We report our quality improvement data that was collected during the first year of workshop implementation. METHODS: We devised a structured half-day arthrocentesis workshop for rheumatology fellows as well as rotating internal medicine residents. This program consisted of a one hour lecture immediately followed by a hands-on workshop that used mannequin models for 5 anatomic sites. A self-assessment questionnaire and medical knowledge test were administered before and after each session. The accuracy of the self-assessment questionnaire was analyzed by comparing responses to an external objective measure of knowledge in the same content area. Finally, an optional postworkshop survey addressed resident satisfaction. RESULTS: Thirty-eight trainees participated in the workshop between July 2006 and June 2007. There were statistically significant improvements in self-confidence in 9 content areas (P < 0.0002), cognitive testing (P < 0.0001) and in self-assurance of procedural skill at all anatomic sites. A high degree of discordance was found between the perceived level of competence and the actual performance on the medical knowledge test during the preworkshop analysis. In contrast, the postworkshop analysis displayed modestly higher concordance. All residents completing a postworkshop survey believed that it was a useful exercise, and 96% stated that they would change their practice habits. CONCLUSION: The arthrocentesis workshop provided a solid foundation from which trainees can learn key concepts of joint injection, increase their self-confidence and refine their motor skills. The accuracy of resident self-reported confidence is poor and should therefore be used only to complement other means of competency assessment and medical knowledge acquisition.

Simplified system for absolute fracture risk assessment: clinical validation in Canadian women.

Absolute 10-yr fracture risk based on multiple factors is the preferred method for risk assessment. A simplified risk assessment system from sex, age, DXA, and two clinical risk factors (CRFs)--prior fracture and systemic corticosteroid (CS) use--has been used in Canada since 2005. This study was undertaken to evaluate this system in the Canadian female population. A total of 16,205 women > or =50 yr of age at the time of baseline BMD (1998-2002) were identified in a database containing all clinical DXA test results for the Province of Manitoba, Canada. Basal 10-yr fracture risk from age and minimum T-score (lumbar spine, femur neck, trochanter, total hip) was categorized as low (<10%), moderate (10-20%), or high (>20%). Health service records since 1987 were assessed for prior fracture codes (N = 5224), recent major CS use (N = 616), and fracture codes after BMD testing (mean, 3.1 yr of follow-up) for the hip, vertebrae, forearm, or humerus (designated osteoporotic, N = 757). Fracture risk predicted from age and minimum T-score alone showed a significant gradient in observed fracture rates (low 5.1 [95% CI, 4.1-6.4], moderate 11.5 [95% CI, 10.1-13.0], high 25.4 [95% CI, 23.2-27.9] per 1000 person-years; p-for-trend <0.0001). There was an incremental increase in incident fracture rates from a prior fracture (13.9 [95% CI, 11.3-16.4] per 1000 person-years) or major CS use (11.2 [95% CI, 4.1-18.2] per 1000 person-years). This simplified fracture risk assessment system provides an assessment of fracture risk that is consistent with observed fracture rates.

Phonon populations and electrical power dissipation in carbon nanotube transistors.

Carbon nanotubes and graphene are candidate materials for nanoscale electronic devices. Both materials show weak acoustic phonon scattering and long mean free paths for low-energy charge carriers. However, high-energy carriers couple strongly to optical phonons, which leads to current saturation and the generation of hot phonons. A non-equilibrium phonon distribution has been invoked to explain the negative differential conductance observed in suspended metallic nanotubes, while Raman studies have shown the electrical generation of hot G-phonons in metallic nanotubes. Here, we present a complete picture of the phonon distribution in a functioning nanotube transistor including the G and the radial breathing modes, the Raman-inactive zone boundary K mode and the intermediate-frequency mode populated by anharmonic decay. The effective temperatures of the high- and intermediate-frequency phonons are considerably higher than those of acoustic phonons, indicating a phonon-decay bottleneck. Most importantly, inclusion of scattering by substrate polar phonons is needed to fully account for the observed electronic transport behaviour.

Energy dissipation in graphene field-effect transistors.

We measure the temperature distribution in a biased single-layer graphene transistor using Raman scattering microscopy of the 2D-phonon band. Peak operating temperatures of 1050 K are reached in the middle of the graphene sheet at 210 kW cm(-2) of dissipated electric power. The metallic contacts act as heat sinks, but not in a dominant fashion. To explain the observed temperature profile and heating rate, we have to include heat flow from the graphene to the gate oxide underneath, especially at elevated temperatures, where the graphene thermal conductivity is lowered due to umklapp scattering. Velocity saturation due to phonons with about 50-60 meV energy is inferred from the measured charge density via shifts in the Raman G-phonon band, suggesting that remote scattering (through field coupling) by substrate polar surface phonons increases the energy transfer to the substrate and at the same time limits the high-bias electronic conduction of graphene.

Doppler sonographic criteria for the diagnosis of inferior mesenteric artery stenosis.

OBJECTIVE: The purpose of this study was to define the optimal Doppler criteria for the diagnosis of inferior mesenteric artery (IMA) stenosis in patients with suspected chronic mesenteric ischemia (CMI). METHODS: A retrospective review of 205 dedicated color and pulsed Doppler sonographic studies of mesenteric arteries was performed in 205 patients. All studies were performed in patients with suspected CMI. Correlative angiography was available in 50 patients. RESULTS: The IMA was visualized in 176 of 205 Doppler sonographic examinations (86%) and in 92% of the correlative studies. The visualization rate for the detection of a patent IMA by Doppler sonography in this series was 90%. The ranges of the peak systolic velocity (PSV), end-diastolic velocity (EDV), and mesenteric-aortic velocity ratio (MAR) in the nonstenotic IMA were 70 to 200 cm/s, 0 to 33 cm/s, and 0.7 to 3.7, respectively. The ranges of the PSV, EDV, and MAR in IMA stenosis were 200 to 485 cm/s, 0 to 177 cm/s, and 0.69 to 8.1. The threshold values for severe IMA stenosis by logistic regression analysis (n = 42) were as follows: PSV, greater than 200 cm/s; EDV, greater than 25 cm/s; and MAR, greater than 2.5, with sensitivities of 90%, 40%, and 80%; specificities of 97%, 91%, and 88%; positive predictive values (PPVs) of 90%, 57%, and 67%; negative predictive values (NPVs) of 97%, 83%, and 93%; and accuracy of 95%, 79%, and 86%, respectively. CONCLUSIONS: We found that a PSV of greater than 200 cm/s was the best criterion for the diagnosis of IMA stenosis. The sensitivity, specificity, PPV, NPV, and accuracy for the PSV were 90%, 97%, 90%, 97%, and 95%, respectively.

Photocurrent imaging and efficient photon detection in a graphene transistor.

We measure the channel potential of a graphene transistor using a scanning photocurrent imaging technique. We show that at a certain gate bias, the impact of the metal on the channel potential profile extends into the channel for more than one-third of the total channel length from both source and drain sides; hence, most of the channel is affected by the metal. The potential barrier between the metal-controlled graphene and bulk graphene channel is also measured at various gate biases. As the gate bias exceeds the Dirac point voltage, VDirac, the original p-type graphene channel turns into a p-n-p channel. When light is focused on the p-n junctions, an impressive external responsivity of 0.001 A/W is achieved, given that only a single layer of atoms are involved in photon detection.

Chemical doping and electron-hole conduction asymmetry in graphene devices.

We investigate poly(ethylene imine) and diazonium salts as stable, complementary dopants on graphene. Transport in graphene devices doped with these molecules exhibits asymmetry in electron and hole conductance. The conductance of one carrier is preserved, while the conductance of the other carrier decreases. Simulations based on nonequilibrium Green's function formalism suggest that the origin of this asymmetry is imbalanced carrier injection from the graphene electrodes caused by misalignment of the electrode and channel neutrality points.