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Atomically precise graphene nanoribbons (GNRs) synthesized from the bottom-up exhibit promising electronic properties for high-performance field-effect transistors (FETs). The feasibility of fabricating FETs with GNRs (GNRFETs) has been demonstrated, with ongoing efforts aimed at further improving their performance. However, their long-term stability and reliability remain unexplored, which is as important as their performance for practical applications. In this work, we fabricated short-channel FETs with nine-atom-wide armchair GNRs (9-AGNRFETs). We revealed that the on-state (ION) current performance of the 9-AGNRFETs deteriorates significantly over consecutive full transistor on and off logic cycles, which has neither been demonstrated nor previously considered. To address this issue, we deposited a thin ∼10 nm thick atomic layer deposition (ALD) layer of aluminum oxide (Al2O3) directly on these devices. The integrity, compatibility, electrical performance, stability, and reliability, of the GNRFETs before and/or after Al2O3 deposition were comprehensively studied. The results indicate that the observed decline in electrical device performance is most likely due to the degradation of contact resistance over multiple measurement cycles. We successfully demonstrated that the devices with the Al2O3 layer operate well up to several thousand continuous full cycles without any degradation. Our study offers valuable insights into the stability and reliability of GNR transistors, which could facilitate their large-scale integration into practical applications.

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Background: Traditional health economic evaluations of antimicrobials currently underestimate their value to wider society. They can be supplemented by additional value elements including insurance value, which captures the value of an antimicrobial in preventing or mitigating impacts of adverse risk events. Despite being commonplace in other sectors, constituents of the impacts and approaches for estimating insurance value have not been investigated. Objectives: This study assessed the insurance value of a novel gram-negative antimicrobial from operational healthcare, wider population health, productivity, and informal care perspectives. Methods: A novel mixed-methods approach was used to model insurance value in the United Kingdom: (1) literature review and multidisciplinary expert workshops to identify risk events for 4 relevant scenarios: ward closures, unavoidable shortage of conventional antimicrobials, viral respiratory pandemics, and catastrophic antimicrobial resistance (AMR); (2) parameterizing mitigable costs and frequencies of risk events across perspectives and scenarios; (3) estimating insurance value through a Monte Carlo simulation model for extreme events and a dynamic disease transmission model. Results: The mean insurance value across all scenarios and perspectives over 10 years in the UK was £718 million, should AMR remain unchanged, where only £134 million related to operational healthcare costs. It would be 50%-70% higher if AMR steadily increased or if a more risk-averse view (1-in-10 year downside) of future events is taken. Discussion: The overall insurance value if AMR remains at current levels (a conservative projection), is over 5 times greater than insurance value from just the operational healthcare costs perspective, traditionally the sole perspective used in health budgeting. Insurance value was generally larger for nationwide or universal (catastrophic AMR, pandemic, and conventional antimicrobial shortages) rather than localized (ward closure) scenarios, across perspectives. Components of this insurance value match previously published estimates of operational costs and mortality impacts. Conclusions: Insurance value of novel antimicrobials can be systematically modeled and substantially augments their traditional health economic value in normal circumstances. These approaches are generalizable to similar health interventions and form a framework for health systems and governments to capture broader value in health technology assessments, improve healthcare access, and increase resilience by planning for adverse scenarios.

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Background and Aim: Eosinophilic esophagitis (EoE) is a chronic disease which may progress to a fibro-stenotic phenotype due to esophageal sub-epithelial fibrosis. Esophageal wall thickening in patients with EoE has been demonstrated in a few studies using endoscopic ultrasound (EUS). The aim of this study was to longitudinally assess the endoscopic appearance, wall thickness, histology, and dysphagia score of EoE patients. Methods: Patients with EoE were recruited and studied between February 2012 and April 2021. Patients were evaluated on two separate occasions at least 12 months apart with endoscopy, EUS, and esophageal mucosal biopsies. The dysphagia score and epidemiology data were also assessed. Results: A total of 16 EoE patients were included with a mean follow-up duration of 2.2 ± 1.2 years. In 14/16 (88%) patients, the total wall thickness of the distal esophagus significantly increased (P = 0.0012) as a result of thickening of the muscularis propria (P = 0.0218). However, only 1/14 (7%) patient had an increase in the dysphagia score, while 8/14 (57%) and 5/14 (36%) had a stable and reduced dysphagia score, respectively. No differences were found in the total thickness of other esophageal regions, dysphagia score, endoscopic appearance, and eosinophil count over time. Conclusion: Distal esophageal wall thickness increases with time in EoE patients, independent of the dysphagia score and eosinophil count.

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BACKGROUND: Thickening of the esophageal wall in patients with eosinophilic esophagitis (EoE) and gastro-esophageal reflux disease (GERD) has been shown in studies using endoscopic ultrasound (EUS). We hypothesise that transmural inflammation in EoE results in prominent esophageal wall thickening compared with the mucosal inflammation in GERD. The aim of this study was to compare the relationship among dysphagia, endoscopic appearance, wall thickness, histology, and motility in EoE and GORD. METHODS: EoE and GERD patients were prospectively studied between February 2012 and April 2021. Patients were studied on 2 separate occasions with endoscopy, EUS and mucosal biopsies, followed by high-resolution manometry. Epidemiology and dysphagia data were obtained. RESULTS: A total of 45 patients (31 EoE, 14 GERD) were included. There were no significant differences in age, sex, duration of disease and presence of esophageal motility disorders. EoE patients had a higher dysphagia score (P < 0.001), EREFS score (P < 0.001) and peak eosinophil count (P < 0.001) compared with GERD patients. Thickness of the submucosa in the distal esophagus in EoE was significantly higher than GERD (P = 0.003) and positively correlated with duration of disease (P = 0.01, R = 0.67). Positive correlation was also found between dysphagia score and distal total esophageal wall thickness (P = 0.03, R = 0.39) in EoE patients. No correlation was found between these variables in GERD patients. CONCLUSION: Distal esophageal wall thickness positively correlates with dysphagia score in EoE but not GERD. This appears to be related to the composition of the submucosa which can be identified using EUS.

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BACKGROUND AND AIM: The prevalence and incidence of eosinophilic esophagitis (EoE) has been increasing over recent years. However, the natural history remains incompletely understood particularly the differences in disease characteristics and progression of childhood-onset and adult-onset EoE. The aim of this study was to evaluate the disease characteristics and progression of childhood-onset and adult-onset EoE. METHODS: A cross-sectional, questionnaire-based study, on 87 adults and 67 children from 2 major tertiary hospitals in South Australia was conducted. Data of those who were diagnosed with EoE between 1999 and 2018 were collected and correlated with medical records. RESULTS: Of the 87 adults with EoE, 34 (39%) were diagnosed at the age of < 18 years (childhood-onset EoE). Reflux symptoms were more common in childhood-onset EoE, whereas asthma was more common in adult-onset EoE. The median duration of symptoms prior to diagnosis of EoE was > 1-4 years in childhood-onset disease (44%) and ≥ 10 years in adult-onset disease (34%). Food impaction was significantly more common on initial presentation in those with adult-onset EoE, whereas weight loss was more common in childhood-onset EoE. At the time of questionnaire, regurgitation, abdominal pain, and bloating were more common in childhood-onset EoE. Those with childhood-onset EoE were more likely to have multiple symptoms at questionnaire when compared with their adult-onset counterparts. In both groups, 15% (5/34 childhood-onset EoE and 8/53 adult-onset EoE) were asymptomatic at the time of questionnaire. CONCLUSION: Childhood-onset EoE appears to be a progressive disease from childhood to adulthood, however with more inflammatory-type symptoms post transition compared to those with adult-onset EoE.

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Dysphagia is a common problem affecting all ages. It is increasing in frequency particularly among the younger population due to the rising incidence of eosinophilic oesophagitis, a condition which often leads to acute presentation to hospital for the first time with food bolus obstruction requiring endoscopic removal. Careful history taking remains the first and most important step in evaluating dysphagia, and it is especially important to distinguish an oropharyngeal versus oesophageal origin, which helps to guide further investigation and therapy. The three main investigations for dysphagia remain endoscopy, barium study and manometry, with endoscopy also offering therapeutic potential. Management is largely determined by the eventual diagnosis, often in a multi-disciplinary setting.

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INTRODUCTION: Night-time gastroesophageal reflux (nGER) symptoms are commonly associated with interrupted sleep. Most studies attempting to understand the relationship between sleep, arousal, and nGER events have been performed so using accelerometry; however, this technology is limited in its ability to precisely determine the temporal association between sleep and reflux events. We aimed to examine the temporal relationships between nGER events and arousal/awakening from sleep using high resolution, in-laboratory polysomnography (PSG). METHODS: Individuals between 18 and 70 years who had undergone a gastroscopy within 12 months underwent simultaneous 24-hour pH/impedance monitoring and in-laboratory PSG. The temporal relationship between each nGER event and sleep/arousals/awakenings was determined for each participant. Analyses were limited to the sleep period (between "lights out" and time of final waking). RESULTS: Analyses were conducted on the data from 25 individuals, 64% of whom had nGER episodes (5 ± 5 events per person, range 1-18) and 64% of whom had obstructive sleep apnea (OSA, mean apnea-hypopnea index 20 ± 11 events/hr, range 6-44). There were no differences in PSG-determined sleep duration, sleep efficiency, sleep architecture, arousals/awakenings, or sleep apnea severity between those with nGER and those without. Most nGER events (82%) occurred during a PSG epoch that had been classified as wake. Arousals/awakenings preceded almost all events (73/76), whereas fewer had an arousal/awakening after the event (15/76). DISCUSSION: As opposed to what is typically assumed, nGER does not seem to cause arousal from sleep, but rather arousal from sleep predisposes to nGER.

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Eosinophilic oesophagitis (EoE) and gastro-oesophageal reflux disease (GORD) are the most common causes of chronic oesophagitis and dysphagia associated with oesophageal mucosal eosinophilia. Distinguishing between the two is imperative but challenging due to overlapping clinical and histological features. A diagnosis of EoE requires clinical, histological and endoscopic correlation whereas a diagnosis of GORD is mainly clinical without the need for other investigations. Both entities may exhibit oesophageal eosinophilia at a similar level making a histological distinction between them difficult. Although the term proton-pump inhibitor responsive oesophageal eosinophilia has recently been retracted from the guidelines, a relationship between EoE and GORD still exists. This relationship is complex as they may coexist, either interacting bidirectionally or are unrelated. This review aims to outline the differences and potential relationship between the two conditions, with specific focus on histology, immunology, pathogenesis and treatment.

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In this article, the current author tells the story of an unexpected musical memorial he and his fellow band mates performed as a tribute to a man named Gordon "Gizmo," a husband and father. (PsycINFO Database Record

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BACKGROUND & AIMS: Achalasia is a disorder of esophageal motility with a reported incidence of 0.5 to 1.6 per 100,000 persons per year in Europe, Asia, Canada, and America. However, estimates of incidence values have been derived predominantly from retrospective searches of databases of hospital discharge codes and personal communications with gastroenterologists, and are likely to be incorrect. We performed a cohort study based on esophageal manometry findings to determine the incidence of achalasia in South Australia. METHODS: We collected data from the Australian Bureau of Statistics on the South Australian population. Cases of achalasia diagnosed by esophageal manometry were identified from the 3 adult manometry laboratory databases in South Australia. Endoscopy reports and case notes were reviewed for correlations with diagnoses. The annual incidence of achalasia in the South Australian population was calculated for the decade 2004 to 2013. Findings were standardized to those of the European Standard Population based on age. RESULTS: The annual incidence of achalasia in South Australia ranged from 2.3 to 2.8 per 100,000 persons. The mean age at diagnosis was 62.1 ± 18.1 years. The incidence of achalasia increased with age (Spearman rho, 0.95; P < .01). The age-standardized incidence ranged from 2.1 (95% CI, 1.8-2.3) to 2.5 (95% CI, 2.2-2.7). CONCLUSIONS: Based on a cohort study of esophageal manometry, we determined the incidence of achalasia in South Australia to be 2.3 to 2.8 per 100,000 persons and to increase with age. South Australia's relative geographic isolation and the population's access to manometry allowed for more accurate identification of cases than hospital code analyses, with a low probability of missed cases.

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IMPORTANCE: The Medical Student Performance Evaluation (MSPE)--formerly called the dean's letter--is an important tool for residency program directors to use in assessing student qualifications for both invitation to interview and construction of their rank order list. Many institutions are now allowing students to construct their own Unique Characteristics (UC) section for the MSPE. This study addresses the results of allowing students to construct their own UC. OBJECTIVES: The goal of this study was to allow students to voice their thoughts regarding their participation in the construction of the UC section of the MSPE. The survey evaluated student attitude toward, value of, and support for the UC section. METHOD: We conducted a cross-sectional survey of all fourth-year medical students at the Medical College of Wisconsin during the 2014-2015 academic year. Responses were received from 66% of students (133 out of 199). We developed a question bank to cover the aims of the study--to assess student perceived value, experience writing, and support for the UC section. RESULTS: There was agreement among students that their participation will positively affect their candidacy for interview selection and success in the match. Overall significance of regression model P = .001, R2. = .60. Additionally, students believed they had an advantage over applicants at other schools without the opportunity to draft their UC. Other findings included that men found the task more challenging, psychiatry applicants were least satisfied with the character count, and emergency medicine applicants voiced the lowest value for the UC section. CONCLUSIONS: The present study supports, in general terms, the utility and value of students drafting their own UC section of the MSPE. Future investigations should focus on expanding to other schools, comparing public to private institutions, and refining the interspecialty comparisons.

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PURPOSE: Using a quasi-experimental approach, we examined student and faculty satisfaction with a mock residency interview program. We also examined whether self-selected participants had match rates that differed from nonparticipants. METHODS: Interviews were arranged on a specified evening between students and a physician in the specialty to which the student wished to apply. Interviews were structured as similarly to residency interviews as possible, but included 10 minutes of verbal feedback and subsequent written feedback to all students. Students completed surveys indicating their satisfaction with the mock interview immediately following the interview and 5 months later (after their actual resident interviews). Faculty feedback to students and their satisfaction with the program also was collected. Out of 189 (55%) students in the senior class, 104 volunteered to participate. RESULTS: Immediately following the mock interview, over 90% of students who participated either strongly agreed or agreed that the interview feedback was helpful, seemed realistic, and helped them identify strengths and weaknesses. Responses collected 5 months later were still favorable, but less positive. Faculty identified 7 students who they believed had poor interview techniques and an additional 13 who interviewers believed would be unlikely to match in their specialty. Final match results for the group participating in the mock interview showed a primary match rate of 99%, which was higher than students who did not participate (94%, P < .001). CONCLUSION: In a self-selected group of students who chose to participate, mock interviews were useful in improving student match success compared to students who did not participate in the mock interview program. Because all students were not required to participate, it is unclear whether this tactic would be successful for all students.

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Achalasia is a motility disorder encountered by surgeons during the investigation and treatment of dysphagia. Recent advances in manometry technology, a widely accepted new classification system and a new treatment rapidly gaining international acceptance, have changed the working knowledge required to successfully manage patients with achalasia. We review the Chicago classification subtypes of achalasia with type II achalasia being a predictor of success and type III achalasia a predictor of treatment failure. We review per-oral endoscopic myotomy as an emerging treatment option and its potential for improving the treatment of type III achalasia.

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PROBLEM: Every graduating medical student must write a personal statement for the Electronic Residency Application Service (ERAS), yet there are no widely available resources designed to aid the writing process, causing stress among applicants. APPROACH: The authors offered every Medical College of Wisconsin senior student in the Classes of 2014 and 2015 a voluntary self-contained two-hour Residency Application Personal Statement Writers Workshop. The session included the selection of writing prompts, speedwriting, and a peer-edit critique. Data were gathered before and after each workshop and at the time of ERAS submission. OUTCOMES: One hundred nine students elected to participate. Of the 96 participants completing a preworkshop questionnaire, only 28 (29%) were comfortable with creative and reflective writing. Fifty-four students completed a follow-up survey after submitting their ERAS application. Fifty-one (94%) found the session effective in getting their personal statement started, and 65 (70%) were surprised by the quality of their writing. Almost all could trace some of their final statement to the workshop. Forty-six (85%) found working with other students helpful, and 49 (91%) would recommend the session to future students; 47 (87%) agreed that the workshop was "fun." NEXT STEPS: The full workshop will be repeated yearly. Workshops will also be offered to residents preparing fellowship applications. A shorter version (without the peer-edit critique) was used successfully with the entire Class of 2016 to help them reflect on their initial clinical encounters. The authors will seek further opportunities to enhance reflection for students, residents, and faculty with these techniques.

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BACKGROUND: With proton pump inhibitors and current sophisticated endoscopic techniques, the number of patients requiring surgical intervention for upper gastrointestinal bleeding has decreased considerably while trans-arterial embolization is being used more often. There are few direct comparisons between the effectiveness of surgery and embolization. METHODS: A retrospective study of patients from two Australian teaching hospitals who had surgery or trans-arterial embolization (n = 103) for severe upper gastrointestinal haemorrhage between 2004 and 2012 was carried out. Patient demographics, co-morbidities, disease pathology, length of stay, complications, and overall clinical outcome and mortality were compared. RESULTS: There were 65 men and 38 women. The median age was 70 (range 36-95) years. Patients requiring emergency surgical intervention (n = 79) or trans-arterial embolization (n = 24) were compared. The rate of re-bleeding after embolization (42%) was significantly higher compared with the surgery group (19%) (P = 0.02). The requirement for further intervention (either surgery or embolization) was also higher in the embolization group (33%) compared with the surgery group (13%) (P = 0.03). There was no statistical difference in mortality between the embolization group (5/24, 20.8%) and the surgical group (13/79, 16.5%) (P = 0.75). CONCLUSION: Emergency surgery and embolization are required in 2.6% of patients with upper gastrointestinal bleeding. Both techniques have high mortalities reflecting the age, co-morbidities and severity of bleeding in this patient group.

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AIM: To evaluate the practice of nutritional assessment and management of hospitalised patients with cirrhosis and the impact of malnutrition on their clinical outcome. METHODS: This was a retrospective cohort study on patients with liver cirrhosis consecutively admitted to the Department of Gastroenterology and Hepatology at the Royal Adelaide Hospital over 24 mo. Details were gathered related to the patients' demographics, disease severity, nutritional status and assessment, biochemistry and clinical outcomes. Nutritional status was assessed by a dietician and determined by subjective global assessment. Estimated energy and protein requirements were calculated by Simple Ratio Method. Intake was estimated from dietary history and/or food charts, and represented as a percentage of estimated daily requirements. Median duration of follow up was 14.9 (0-41.4) mo. RESULTS: Of the 231 cirrhotic patients (167 male, age: 56.3 ± 0.9 years, 9% Child-Pugh A, 42% Child-Pugh B and 49% Child-Pugh C), 131 (57%) had formal nutritional assessment during their admission and 74 (56%) were judged to have malnutrition. In-hospital caloric (15.6 ± 1.2 kcal/kg vs 23.7 ± 2.3 kcal/kg, P = 0.0003) and protein intake (0.65 ± 0.06 g/kg vs 1.01 ± 0.07 g/kg, P = 0.0003) was significantly reduced in patients with malnutrition. Of the malnourished cohort, 12 (16%) received enteral nutrition during hospitalisation and only 6 (8%) received ongoing dietetic review and assessment following discharge from hospital. The overall mortality was 51%, and was higher in patients with malnutrition compared to those without (HR = 5.29, 95%CI: 2.31-12.1; P < 0.001). CONCLUSION: Malnutrition is common in hospitalised patients with cirrhosis and is associated with higher mortality. Formal nutritional assessment, however, is inadequate. This highlights the need for meticulous nutritional evaluation and management in these patients.

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BACKGROUND AND STUDY AIMS: Colonoscopy with inhaled methoxyflurane (Penthrox) is well tolerated in unselected subjects and is not associated with respiratory depression. The aim of this prospective study was to compare the feasibility, safety, and post-procedural outcomes of portable methoxyflurane used as an analgesic agent during colonoscopy with those of anesthesia-assisted deep sedation (AADS) in subjects with morbid obesity and/or obstructive sleep apnea (OSA). PATIENTS AND METHODS: The outcomes of 140 patients with morbid obesity/OSA who underwent colonoscopy with either Penthrox inhalation (n = 85; 46 men, 39 women; mean age 57.2 ±â€Š1.1 years) or AADS (n = 55; 27 men, 28 women; mean age, 54.9 ±â€Š1.1 years) were prospectively assessed. RESULTS: All Penthrox-assisted colonoscopies were successful, without any requirement for additional intravenous sedation. Compared with AADS, Penthrox was associated with a shorter total procedural time (24 ±â€Š1 vs. 52 ±â€Š1 minutes, P < 0.001), a lower incidence of hypotension (3 /85 vs. 23 /55, P < 0.001), and a lower incidence of respiratory desaturation (0 /85 vs. 14 /55, P < 0.001). The patients in the Penthrox group recovered more rapidly and were discharged much earlier than those in the AADS group (27 ±â€Š2 vs. 97 ±â€Š5 minutes, P < 0.0001). Of those who underwent colonoscopy with Penthrox, 90 % were willing to receive Penthrox again for colonoscopy. More importantly, of the patients who underwent colonoscopy with Penthrox and had had AADS for previous colonoscopy, 82 % (28 /34) preferred to receive Penthrox for future colonoscopies. Penthrox-assisted colonoscopy cost significantly less than colonoscopy with AADS ($ 332 vs. $ 725, P < 0.001), with a cost saving of approximately $ 400 for each additional complication avoided. CONCLUSIONS: Compared with AADS, Penthrox is highly feasible and safe in patients with morbid obesity/OSA undergoing colonoscopy and is associated with fewer cardiorespiratory complications. Because of the advantages of this approach in regard to procedural time, recovery time, and cost benefit in comparison with AADS, further evaluation in a randomized trial is warranted.

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BACKGROUND: Bleeding peptic ulcer (BPU) frequently occurs in the absence of preceding dyspeptic symptoms. We have observed that patients with BPU had a diminished symptom response to nutrient challenge test compared to uncomplicated peptic ulcer disease (uPUD). We postulated that more symptoms are manifest in patients with uPUD than BPU because there are greater derangements in gastric motor function. AIM: To assess gastric emptying in patients with BPU, uPUD and healthy controls (HC). METHODS: We studied 17 patients with BPU, 10 with uPUD, and 15 HC. After an 8-hour fast, subjects ingested 200 ml of an enteral feeding solution, containing 5 MBq (99m)Tc-rhenium sulphide colloid, every 5 min up to a cumulative volume of 800 ml. Gastric emptying was measured by scintigraphy for the total, proximal and distal stomach. RESULTS: Patients with uPUD had significantly higher gastric retention in the proximal and total stomach at 100 min than HC and BPU, while BPU had similar percent retention to HC. Patients with uPUD had significantly higher cumulative symptom response to the nutrient challenge than did HC and BPU, while BPU had similar symptom responses to HC. CONCLUSIONS: Patients with uPUD have significantly delayed gastric emptying compared to HC and BPU. Data suggest that in addition to alterations of visceral sensory function, altered gastric motor function occurs during a nutrient challenge in uPUD but not BPU. Gastric motor function may contribute to the manifestation of dyspeptic symptoms in PUD.

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PURPOSE OF REVIEW: Combined impedance-manometry was introduced just over 20 years ago for the assessment of esophageal motor function. Since then, technical developments have led to the introduction of high-resolution impedance-manometry (HRIM). However, analysis of the impedance and manometry recordings has remained separate and relatively unchanged since the introduction of HRIM, and it is unclear whether the addition of impedance has had a significant impact on the management of esophageal motor disorders. RECENT FINDINGS: The major technical advance over the past 12 months or so has been the development of automated impedance-manometry (AIM) analysis, in which the impedance and manometric data are analyzed together to assess the interactions between pressure and flow. This analysis has revealed subtle abnormalities in esophageal function in patients with nonobstructive dysphagia who have normal manometry and conventional impedance analyses. AIM analysis has also revealed preoperative characteristics in patients that may predict the occurrence of postfundoplication dysphagia. SUMMARY: Through ongoing technical development, impedance-manometry is becoming increasingly useful clinically to assess esophageal motility disorders as well as to provide further insights into esophageal physiology.

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