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Klinefelter syndrome (KS) frequently causes skeletal fragility characterized by profound alterations in bone microstructure with increased risk of fractures. Increased body fat mass associated with decreased body lean mass are frequent features of KS with possible detrimental effects on skeletal health. In this cross-sectional study, we evaluated the associations between body composition parameters, vertebral fractures (VFs) and trabecular bone score (TBS) in adult subjects with KS.Seventy-one adult males (median age 41 years, range 18-64) with 47, XXY KS were consecutively enrolled by two Endocrinology and Andrology Units (IRCCS Humanitas Research Hospital in Milan and ASST Spedali Civili in Brescia). Dual-energy X-ray absorptiometry (DXA) was performed to assess bone mineral density (BMD) at lumbar spine, femoral neck and total hip, TBS and body composition. Prevalence of VFs was assessed by quantitative morphometry on lateral spine X-rays.VFs were detected in 14 patients (19.7%), without significant association with low BMD (p = 0.912). In univariate logistic regression analysis, VFs were significantly associated with truncal/leg fat ratio (OR 2.32 per tertile; 95% CI 1.05-5.15; p = 0.038), whereas impaired TBS (detected in 23.4% of subjects) was associated with older age at study entry (p = 0.001) and at diagnosis of disease (p = 0.015), body mass index (BMI; p = 0.001), waist circumference (p = 0.007), fat mass index (FMI; p 0.001), FMI/lean mass index (LMI) ratio (p = 0.001). Prevalence of VFs was not significantly different between subjects with impaired TBS as compared to those with normal TBS (26.7 vs. 18.4%; p = 0.485). Skeletal end-points were not significantly associated with duration of testosterone replacement therapy and serum testosterone and 25hydroxyvitamin D values.Body composition might influence bone quality and risk of VFs in subjects with KS.

Background Coronary artery disease (CAD) is the single leading cause of mortality, premature death, and morbidity worldwide. Artificial intelligence (AI) could help identify markers present within first-line diagnostic imaging routinely performed in patients referred for suspected angina, such as chest radiographs. Purpose To train, test, and validate a deep learning (DL) algorithm for detecting the presence of significant CAD based on chest radiographs. Methods Data of patients undergoing chest radiography and coronary angiography were retrospectively analysed. A deep convolutional neural network (DCNN) was designed to detect significant CAD from the patient posteroanterior/anteroposterior chest radiograph. The DCNN was trained for binary classification of severe CAD absence/presence (at least one diseased coronary vessel with ≥70% stenosis). Coronary angiography reports were used as the ground truth. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of the DCNN were calculated. Multivariate analysis was performed to identify independent correlation among the presence of significant CAD (dependent variable), DCNN prediction, and CAD risk factors. Results Information of 7728 patients referred for suspected angina was reviewed. Severe CAD was present in 4482 patients (58%; 1% left main, 28% one vessel, 16% two vessels, and 12% 3 vessels). Patients were randomly divided for training (70%; n=5454) and fine-tuning/testing (10%; n=773) of the algorithm. Internal validation was performed with the remaining patients (20%; n=1501). At binary logistic regression, the DCNN prediction was the strongest independent determinant of severe CAD (p Conclusion The chest radiograph is ubiquitous and carries a plethora of information concerning the patient's health status, including direct and indirect signs of CAD. Our DL algorithm can predict, with high sensitivity, the presence of severe CAD in patients referred for suspected angina. It could be used to pre-test significant CAD probability in outpatient clinics, emergency room settings, and CAD screening in more extensive settings. Further studies are required to externally validate the algorithm and develop a clinically applicable tool. Funding Acknowledgement Type of funding sources: None.

Background Cold snare polypectomy (CSP) is widely utilized for resection of small polyps (less than 10mm), due to the technique’s favourable safety profile. However, Hot Snare Endoscopic Mucosal Resection (HSEMR) remains the standard of care for large polyps greater than or equal to 20mm. HSEMR carries an increased risk of complications. These include delayed bleeding, perforation, and post-polypectomy syndrome, along with residual or recurrent adenomatous (RRA). More recently, Cold Snare Endoscopic Mucosal Resection (CSEMR) technique has been used selectively for polyps greater than 20mm. Published studies have demonstrated a significantly lower adverse event rate of complications as compared with HSEMR. RRA utilizing CSP remains a concern, with a recent publication reporting a recurrence of 34.8% on follow-up endoscopy. We present the experience at a single Canadian academic centre with patients undergoing CSEMR for polyps greater than 20mm. Aims To demonstrate the efficacy and safety of cold snare endoscopic mucosal resection CSEMR of large (greater than or equal to 20mm) polyps at a single Canadian academic centre. Methods We retrospectively reviewed colonoscopies performed by endoscopists employing this technique at our centre from January 2020 to August 2021. 15 total cases were identified for patients with polyps greater than or equal to 20 mm, removed by CSEMR technique. Results Patient age ranged from 41 to 76, with a median patient age was 66. There were 10 males and 5 females. There were no adverse events intraoperatively. 15/15 (100%) polyps were successfully resected using CSEMR technique. Polyp size ranged from 2 cm to 7 cm, and there was a median polyp size of 3 cm. 14/15 (93%) polyps were proximal to the splenic flexure, with 1/15 (7%) polyp in the rectum. 6/15 (40%) patients received snare tip soft coagulation to the edges of the polypectomy site. Polyp histology included 7 tubular adenomas, 3 tubulovillous adenomas, 4 sessile serrated polyps, and one hyperplastic polyp. Two patients were on aspirin 81 mg daily, and there were zero patients on any other antiplatelets or anticoagulation. 1/15 patient presented with late bleeding requiring emergent colonoscopy. There were no immediate or delayed perforations or other serious adverse events recorded. Approximately 50% of patients have had follow-up colonoscopy within 3–6 months of their initial procedure. Follow-up ranged from 12 to 252 days, with a median time to follow up of 171 days. 3/7 (43%) patients had histologic evidence of recurrence at follow-up colonoscopy, all of which were successfully treated endoscopically. Conclusions Selective CSEMR is a safe and effective technique, with a low risk of complications. There may be a higher rate of residual polyp at follow-up colonoscopy compared to HSEMR. This data will need further validation with a larger sample size. Funding Agencies None

Transcranial alternating current stimulation (TACS) is commonly used to synchronise the output of a cortical area to other parts of the nervous system, but evidence for this based on brain recordings in humans is challenging. The brain transmits beta oscillations (~21Hz) to tonically contracted limb muscles linearly and through the fastest corticospinal pathways. Therefore, muscle activity may be used as a proxy measure for the level of beta entrainment in the corticospinal tract due to TACS over motor cortex. Here, we assessed if TACS is able to modulate the neural inputs to muscles, which would provide an indirect evidence for TACS-driven neural entrainment. In the first part of this study, we ran a series of simulations of motor neuron (MN) pools receiving inputs from corticospinal neurons with different levels of beta entrainment. Results indicated that MNs should be highly sensitive to changes in corticospinal beta activity. Then, we ran experiments on healthy human subjects (N=10) in which TACS (at 1mA) was delivered over the motor cortex at 21Hz (beta stimulation), or at 7Hz or 40Hz (control conditions) while the abductor digiti minimi (ADM) or the tibialis anterior muscle (TA) were tonically contracted. Muscle activity was measured using high-density electromyography, which allowed us to decompose the spiking activity of pools of motor units innervating the studied muscles. By analysing motor unit pool activity, we observed that none of the tested TACS conditions could consistently alter the spectral characteristics of the common neural inputs received by the muscles. These results suggest that 1mA-TACS over motor cortex given at frequencies in the beta band does not affect corticospinal beta entrainment.Highlights-TACS is commonly used to entrain the communication between brain regions-It is challenging to find direct evidence supporting TACS-driven neural entrainment-Simulations show that motor neurons are sensitive to corticospinal beta entrainment-Motor unit activity from human muscles does not support TACS-driven entrainment

Since the 2018 IAEA FEC Conference, FTU operations have been devoted to several experiments covering a large range of topics, from the investigation of the behaviour of a liquid tin limiter to the runaway electrons mitigation and control and to the stabilization of tearing modes by electron cyclotron heating and by pellet injection. Other experiments have involved the spectroscopy of heavy metal ions, the electron density peaking in helium doped plasmas, the electron cyclotron assisted start-up and the electron temperature measurements in high temperature plasmas. The effectiveness of the laser induced breakdown spectroscopy system has been demonstrated and the new capabilities of the runaway electron imaging spectrometry system for in-flight runaways studies have been explored. Finally, a high resolution saddle coil array for MHD analysis and UV and SXR diamond detectors have been successfully tested on different plasma scenarios.

Background The impacts of the COVID-19 pandemic have been far reaching and have necessitated many changes to healthcare delivery. At the QEII Health Sciences Center physical space limitations for patient check-in and recovery have restricted outpatient endoscopy to 3 of 4 available endoscopy suites. On June 1, 2020 a new system of central endoscopy triage and coordination for the Division of Digestive Care and Endoscopy (DC&E) was implemented in an effort to increase efficiency and maintain patient access to endoscopy. The components of the RESET (Re-introduce Endoscopy Safely and EfficienTly) Plan included a) a new endoscopy coordinator role to manage a common endoscopy waitlist, endoscopist schedules, and booking clerks, b) a modified triage system to improve waitlist consistency, c) a common endoscopy waitlist with patients booked in the next available appointment regardless of endoscopist, d) discontinuation of fixed endoscopy slots for endoscopists, and e) appointment scheduling no sooner than 4-weeks in advance to minimize no-shows and last-minute cancellations. Aims The aim of this study is to evaluate the impact of the RESET Plan on the efficiency of DC&E endoscopy. Methods A retrospective pre- and post-implementation study evaluating the volume and efficiency of outpatient endoscopy before and after implementation of the RESET Plan. The Pre-RESET period included all procedures performed from June 1, 2019 to October 31, 2019. The Post-RESET period included all procedures performed from June 1, 2020 to October 31, 2020. A separate endoscopy suite and triage system is used for endoscopic retrograde cholangiopancreatography (ERCP) and these cases were excluded. Early effectiveness outcomes were reported including a comparison of the number of endoscopic procedures per week and per list, pre- and post- implementation. Data analysis was primarily descriptive with data expressed as frequencies, means (SD), and proportions (%). Exploratory group comparisons were performed using independent-samples T-Test. Results During the 5-month Pre-RESET period, 2203 endoscopic procedures were performed. During the Post-RESET period a total of 1920 procedures were performed. Due to pandemic restrictions, there was a 29% decrease in available endoscopy lists from 2019 to 2020. There was a 24% increase in the number procedures performed per endoscopy list, from 6.4 to 8.0 (p=0.004, 95% CI 0.52–2.53), pre- and post-RESET. Conclusions While the COVID-19 pandemic has disrupted healthcare delivery, it has also provided an opportunity to implement health system structure and process changes. The RESET Plan resulted in significant gains in efficiency which largely offset losses in endoscopy throughput imposed by COVID-19 pandemic restrictions. Future research will determine what patient and health system factors most significantly impact system efficiency as well as the cost-effectiveness of the RESET Plan. Funding Agencies CAG

Background The COVID-2019 pandemic continues to restrict access to endoscopy, resulting in delays or cancellation of non-urgent endoscopic procedures. A delay in the removal or exchange of plastic biliary stents may lead to stent occlusion with consensus recommendation of stent removal or exchange at three-month intervals [1–4]. We postulated that delayed plastic biliary stent removal (DPBSR) would increase complication rates. Aims We aim to report our single-centre experience with complications arising from DPBSR. Methods This was a retrospective, single-center, observational cohort study. All subjects who had ERCP-guided plastic biliary stent placement in Halifax, Nova Scotia between Dec 2019 and June 2020 were included in the study. DPBSR was defined as stent removal >=90 days from insertion. Four endpoints were assigned to patients: 1. Stent removed endoscopically, 2. Died with stent in-situ (measured from stent placement to documented date of death/last clinical encounter before death), 3. Pending removal (subjects clinically well, no liver enzyme elevation, not expired, endpoint 1 Nov 2020), and 4. Complication requiring urgent reintervention. Kaplan-Meier survival analysis was used to represent duration of stent patency (Fig.1). Results 102 (47.2%) had plastic biliary stents placed between 2/12/2019 and 29/6/2020. 49 (48%) were female, and the median age was 68 (R 16–91). Median follow-up was 167.5 days, 60 (58.8%) subjects had stent removal, 12 (11.8%) died before replacement, 21 (20.6%) were awaiting stent removal with no complications (median 230d, R 30–332), 9 (8.8%) had complications requiring urgent ERCP. Based on death reports, no deaths were related to stent-related complications. 72(70.6%) of patients had stents in-situ for >= 90 days. In this population, median time to removal was 211.5d (R 91-441d). 3 (4.2%) subjects had stent-related complications requiring urgent ERCP, mean time to complication was 218.3d (R 94–441). Stent removal >=90 days was not associated with complications such as occlusion, cholangitis, and migration (p=1.0). Days of stent in-situ was not associated with occlusion, cholangitis, and migration (p=0.57). Sex (p=0.275), cholecystectomy (p=1.0), cholangiocarcinoma (p=1.0), cholangitis (p=0.68) or pancreatitis (p=1.0) six weeks prior to ERCP, benign vs. malignant etiology (p=1.0) were not significantly associated with stent-related complications. Conclusions Plastic biliary stent longevity may have been previously underestimated. The findings of this study agree with CAG framework recommendations [5] that stent removal be prioritized as elective (P3). Limitations include small sample size that could affect Kaplan-Meier survival analysis. Despite prolonged indwelling stent time as a result of COVID-19, we did not observe an increased incidence of stent occlusion or other complications. Funding Agencies None

Background and purpose: Tumefactive multiple sclerosis (TuMS) (i.e., MS onset presenting with tumefactive demyelinating lesions [TDLs]) is a diagnostic and therapeutic challenge. We performed a multicentre retrospective study to describe the clinical characteristics and the prognostic factors of TuMS. Methods: One hundred two TuMS patients were included in this retrospective study. Demographic, clinical, magnetic resonance imaging (MRI), laboratory data and treatment choices were collected. Results: TuMS was found to affect women more than men (female:male: 2.4), with a young adulthood onset (median age: 29.5years, range: 11–68 years, interquartile range [IQR]: 38 years). At onset, 52% of TuMS patients presented with the involvement of more than one functional system and 24.5% of them with multiple TDLs. TDLs most frequently presented with an infiltrative MRI pattern (38.7%). Cerebrospinal fluid immunoglobulin G oligoclonal bands were often demonstrated (76.6%). In 25.3% of the cases, more than one acute-phase treatment was administered, and almost one-half of the patients (46.6%) were treated with high-efficacy treatments. After a median follow-up of 2.3years (range: 0.1–10.7 years, IQR: 3.4 years), the median Expanded Disability Status Scale (EDSS) score was 1.5 (range: 0–7, IQR: 2). Independent risk factors for reaching an EDSS score ≥3 were a higher age at onset (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 1.03–1.14, p&nbsp

The optimum conditions for access to and sustainment of H-mode plasmas and their expected plasma parameters in the pre-fusion power operation 1 (PFPO-1) phase of the ITER research plan, where the additional plasma heating will be provided by 20 MW of electron cyclotron heating, are assessed in order to identify key open R&D issues. The assessment is performed on the basis of empirical and physics-based scalings derived from present experiments and integrated modelling of these plasmas including a range of first-principle transport models for the core plasma. The predictions of the integrated modelling of ITER H-mode plasmas are compared with ITER-relevant experiments carried out at JET (low-collisionality high-current H modes) and ASDEX Upgrade (significant electron heating) for both global H-mode properties and scale lengths of density and temperature profiles finding reasonable agreement. Specific integration issues of the PFPO-1 H-mode plasma scenarios are discussed taking into account the impact of the specificities of the ITER tokamak design (level of ripple, etc).

International audience; This paper presents the Mechanical Ventilator Milano (MVM), a novel intensive therapy mechanical ventilator designed for rapid, large-scale, low-cost production for the COVID-19 pandemic. Free of moving mechanical parts and requiring only a source of compressed oxygen and medical air to operate, the MVM is designed to support the long-term invasive ventilation often required for COVID-19 patients and operates in pressure-regulated ventilation modes, which minimize the risk of furthering lung trauma. The MVM was extensively tested against ISO standards in the laboratory using a breathing simulator, with good agreement between input and measured breathing parameters and performing correctly in response to fault conditions and stability tests. The MVM has obtained Emergency Use Authorization by U.S. Food and Drug Administration (FDA) for use in healthcare settings during the COVID-19 pandemic and Health Canada Medical Device Authorization for Importation or Sale, under Interim Order for Use in Relation to COVID-19. Following these certifications, mass production is ongoing and distribution is under way in several countries. The MVM was designed, tested, prepared for certification, and mass produced in the space of a few months by a unique collaboration of respiratory healthcare professionals and experimental physicists, working with industrial partners, and is an excellent ventilator candidate for this pandemic anywhere in the world

Alemtuzumab is approved for highly active MS and, in Europe, can be employed after other disease-modifying treatments (DMTs) as an escalation approach or first therapeutic option. The occurrence of secondary autoimmune adverse events and infections differs depending on the employed approach.In the manuscript entitled “Alemtuzumab treatment of multiple sclerosis in real-world clinical practice: report from a single Italian center” by di Ioia M. and collaborators, efficacy and safety data of alemtuzumab were evaluated in a real-world MS population. The aim of the article is to describe in detail the unexpected serious adverse events which occurred in this cohort during and after the administration of the alemtuzumab treatment.Adverse events were observed in 45,7% of the patients. These events were ranked as severe in 23% of the patients. We reported, in particular, cases of autoimmune hemolytic anemia (AIHA), pancytopenia, viral hepatitis E and noninfectious meningo-encephalomyelitis. Keywords: Multiple sclerosis, Alemtuzumab, Safety, Adverse events, Secondary autoimmune disorders, Autoimmune hemolytic anemia

Background Alemtuzumab, is a compound approved for highly active MS, and, in Europe, employed after the use of other disease-modifying treatments (DMTs) with an escalation approach or used as a first therapeutic option. The occurrence of secondary autoimmune adverse events and or infections can differ depending on the employed approach. Objective To evaluate the efficacy and safety of alemtuzumab in real-world MS population that encompassed patients previously treated with other DMTs. Methods 35 patients, treated with alemtuzumab in a single MS Center, were followed for at least 36 months. The study investigated the prevalence of patients reaching the phase of the non-active disease (NEDA-3). All the adverse events were also reported, and correlations assessed. Results At the 36-month follow-up, 66,7% of patients achieved the NEDA-3 status, 90,5% of the patients were relapse-free, 85,7% showed no signs of disability progression, nor signs of MRI activity. Adverse events were observed in 45,7% of the patients and ranked as severe in 23% of them. Cases of autoimmune hemolytic anemia (AIHA), pancytopenia, viral hepatitis E, and noninfectious meningo-encephalomyelitis were found and reported. For these complications, the post hoc analysis showed possible interactive factors and causality related to previous DMT treatments. Conclusions In a real-world MS population like the one investigated in our study, alemtuzumab was found to be an effective treatment when employed as an escalation or rescue therapy. The compound exhibits a variable safety profile and frequent adverse events that are likely depending on previous treatments and their impact on the immune system.

First plasma operation in ITER will start after completing the assembly of the tokamak vessel and the installation of the main sub-systems, but prior to the installation of the blanket modules and the divertor cassettes. Utilization of temporary limiters and divertor replacement structures will provide a poloidal and toroidal reference side position to the plasma edge to protect the vacuum vessel and other components already installed during operations. An additional set of mirrors is required to reflect the power injected from the upper launcher towards the plasma resonance for EC-assisted breakdown of the plasma up to a beam dump needed to trap and absorb the power of the beams after crossing the plasma in order to reduce the stray radiation escaping back into the vacuum chamber down to less than 10% of the total power. The quasi-optical system has been designed, with shape and size of the mirrors compliant with the requirements provided by ITER for their installation, realization and plasma performances, resulting in two standard focussing mirrors and one grating mirror. The beam dump consists of a box with five metal plates, the first providing a spreading of the high incident power and the others coated with absorbing material with thickness distribution studied to gradually reduce the power during the multiple reflections inside the box, avoiding damages to the coating itself. This work focuses on the validation of the quasi-optical design of the mirrors and the assessment of the dump performances, based on a multi-bounces model developed ad-hoc for this purpose. The study includes a tolerance analysis for the beam dump to include the effect of uncertainties in the thickness of the absorbing coating and misalignments of the mirrors, to verify the performances of the dump also when operating in different conditions with respect to the nominal ones.

ObjectivesAt the QEII Health Sciences Centre Emergency Department (ED) in Halifax, Nova Scotia, advanced care paramedics (ACPs) perform procedural sedation and analgesia (PSA) for many indications, including orthopedic procedures. We have begun using ACPs as sedationists for emergent upper gastrointestinal (UGI) endoscopy. This study compares ACP-performed ED PSA for UGI endoscopy and orthopedic procedures in terms of adverse events, airway intervention, vasopressor requirement, and PSA medication use.MethodsA data set was built from an ED PSA quality control database matching 61 UGI endoscopy PSAs to 183 orthopedic PSAs by propensity scores calculated using age, gender, and the American Society of Anesthesiologists (ASA) classification. Outcomes assessed were hypotension (systolic BP30 sec), vomiting, arrhythmias, death, airway intervention, vasopressor requirement, and PSA medication use.ResultsUGI endoscopy patients experienced hypotension more frequently than orthopedic patients (OR=4.11, CI: 2.05-8.22) and required airway repositioning less often (OR=0.24, CI: 0.10-0.59). They received ketamine more frequently (OR=15.7, CI: 4.75-67.7) and fentanyl less often (OR=0.30, CI: 0.15-0.63) than orthopedic patients. Four endoscopy patients received phenylephrine, and one required intubation. No patient died in either group.ConclusionsIn ACP-led sedation for UGI endoscopy and orthopedic procedures, adverse events were rare with the notable exception of hypotension, which was more frequent in the endoscopy group. Only endoscopy patients required vasopressor treatment and intubation. We provide preliminary evidence that ACPs can manage ED PSA for emergent UGI endoscopy, although priorities must shift from pain control to hemodynamic optimization.

The ITER Research Plan envision operation around half of the nominal magnetic field (i.e. around B = 2.65 T) as a path to baseline operation. This work discusses constraints on the optimal range of magnetic field, which is bounded in the lower limit by the presence of the third-harmonic electron cyclotron resonance at half field, and on the upper limit by the loss of core heating and current drive. It will be shown that increasing the magnetic field by only 3%, i.e. to 2.75 T, eliminates the third harmonic parasitic absorption without compromising demonstration of access to H-mode, while operating at a magnetic field of 3.0 T - previously proposed for optimal use of the ion cyclotron system - would impair the use of the electron cyclotron system for core-heating and current drive. Operation at 2.65 T would still be possible if the polarization of the equatorial launcher is changed from X-mode to O-mode in the current flattop phase.

Background Severe restrictions on in-person encounters and endoscopic procedures for digestive care have occurred as a result of the COVID-19 pandemic. This has exacerbated pre-existing barriers in access to gastroenterology (GI) care across Nova Scotia (NS) for patients and primary healthcare providers (PHCPs). In response, a provincial PHCP-GI consultative service (GUT LINK) was implemented at a single tertiary care center with the goal of supporting PHCPs in the management of non-urgent GI referral conditions. Aims To implement and evaluate the acceptability, feasibility, appropriateness, and early effectiveness of the GUT LINK PHCP-GI consultation service. Methods This is an ongoing prospective observational cohort study. All referrals received through the EMR-based referral and triage management system between May and November 2020 that were deemed to be amenable to management within primary care with specialist support were returned to the PHCP with the suggestion to arrange a GUT LINK telephone consultation. GUT LINK appointments were scheduled through an administrative support telephone line with the PHCP and a GI specialist. A post-consultation e-questionnaire was distributed to PHCPs who consented to participate. Feasibility (number of and indication for referrals, PHCP participation rates), acceptability and appropriateness (satisfaction, future use, likelihood to recommend) metrics and outcomes (case resolution, re-referrals, proportion requiring endoscopic investigations) were recorded. Patient charts were reviewed to determine whether the patient ultimately required GI speciality care. Analyses were descriptive and expressed as frequencies, means (+/-SD), medians (+/-SE), and proportions (%). Results A total of 45 GUT LINK consultations were completed between May and November 2020. Of these, 20% required GI specialist care and 80% have remained within primary care, with a median follow-up of 101 (+/-9.1) days. The indications for GUT LINK consultation included lower GI symptoms (64%), abnormal imaging or investigations (17%), and upper GI symptoms (19%). To date, 21 PHCP agreed to be contacted for the post-consultation survey and 10 have been completed. All PHCPs reported that GUT LINK consultation was easy to access, while 90% found the advice helpful and 80% reported that that it resolved the issue. Following the GUT LINK appointment, 80% felt they would not need to refer their patient to GI. Conclusions The implementation of GUT LINK was acceptable, feasible, and improved access to specialist support for management of undifferentiated GI symptoms. Future research will focus on comprehensive stakeholder engagement in order to design, implement, and evaluate GUT LINK PHCP care pathways. Funding Agencies CAG

Background Colorectal cancer (CRC) has the third highest cancer incidence for males and females in Canada1. CRC rates are decreasing, likely due to implementation of CRC screening programs and removal of precancerous polyps. In Nova Scotia, management of large (> 2 cm) polyps is varied. Some patients are referred for endoscopic mucosal resection (EMR), while others referred for surgical resection. EMR is effective2 and associated with less morbidity and mortality compared to surgery3. Furthermore, EMR is less expensive than surgery and requires less resources when performed as a day procedure. Management of these polyps are unknown in Canada and are potentially changing with gathering evidence on the safety and effectiveness of EMR. North American and European guidelines recommend EMR for non-invasive colonic polyps as first line management. Aims This projects aim is to determine how large polyps are being treated in a group of FIT positive patients from Nova Scotia. Methods This is a retrospective observational study. The Nova Scotia Colon Cancer screening database was searched for FIT positive patients in 2017. Patients found to have > 2 cm colonic polyps were included. Malignant polyps were excluded. Electronic charts were reviewed to determine method of polyp removal. Endoscopic and histologic polyp information was obtained. Results 196 patients had at least one polyp > 2 cm. Within the central health zone where pathology results were available 78 patients had > 2cm polyps. 13 were excluded for malignancy, one lost to follow up and one patient was miscoded. In total 63 patients were included, 8 of which underwent a surgical resection. Of these surgically resected polyps the average size was 4 cm and 3 cm for the EMR group. The average time to removal was 3 months in the surgical group and one month in the EMR group. The average age was 68 years in the surgical group and 67 years in the EMR group. The endoscopists referring for surgery were 75% surgeon and 25% GI and the endoscopists performing EMR were 45% surgeon and 55% GI. 1 of 8 (12.5%) patients experienced complications (anastomotic leak) in the surgical group and 2 of 56 (3.6%) patients experienced post polypectomy bleeding in the EMR group. Conclusions In this study 12.5% of large nonmalignant polyps found in a group of FIT positive patients from Nova Scotia were removed surgically via resection. Polyps were on average larger by 1 cm in the surgical group and patients experienced a higher rate of complication. This study highlights the need for a structured system of referral and assessment for endoscopic removal of advanced polyps by expert endoscopists, to reduce the number of surgical resections. Additional investigation of additional years, and health zones outside the tertiary central health zone is ongoing. This will help provide more validity to our current data, and allow comparison of academic vs community management of large polyps. Funding Agencies None

Background: Alemtuzumab, approved for multiple sclerosis (MS), can cause secondary autoimmune adverse events including thyroid disorders, immune thrombocytopenia (ITP), and glomerular nephropathies. Non-ITP autoimmune cytopenias are rarely reported. Objective: To report a case of autoimmune hemolytic anemia (AIHA) and nephropathy in a MS patient treated with alemtuzumab. Case report: A 34-year-old man with MS developed albuminuria and AIHA after the first and only alemtuzumab treatment, with positive Coombs’ direct and indirect tests and IgG autoantibodies. Both AIHA and nephropathy resolved 1 month after treatment with steroids and intravenous immunoglobulins. Conclusion: Our report adds to literature on AIHA and nephropathy after alemtuzumab treatment and suggests to add Coombs’ tests to the screening panel required for alemtuzumab treatment.

Mechanical vibration applied directly to the muscle belly or tendon has been reported to elicit a specific reflex loop named tonic vibration reflex (TVR), which involves motor unit (MU) activation synchronized and un-synchronized within the vibration cycle. Indirect application of vibration to the muscle by vibration exercise (VE) has also been suggested to evoke TVR, as evidenced by the spectral peaks observed at the vibration frequency in the surface electromyography (sEMG). However, other studies interpreted these spectral peaks as the result of motion artifacts (MAs). The aim of the present study is, therefore, to investigate MU activation patterns during VE in order to clarify the nature of those spectral peaks. To this end, low-intensity isometric contractions were executed with and without VE, and high-density sEMG measurements were performed during the contraction tasks. MU action potential (MUAP) trains were extracted by decomposing the recorded high-density sEMG signals. The spectra of the MUAP trains were then calculated and compared between vibration and no-vibration conditions. Clear MU synchronization was observed during VE, confirming the spectral peaks at the vibration frequency to be mainly due to the reflex loop rather than MAs.

The ITER ECRH system consists of 24 gyrotrons with up to 24 MW installed millimeter wave heating power at 170 GHz, power supplies, control system, transmission lines, one Equatorial and the four Upper Launchers. With its high frequency and small beam focus the ECRH has the unique capability of driving locally current. While the Equatorial Launcher mainly acts for central heating and current profile shaping, the Upper Launchers aim on suppressing MHD instabilities, especially neoclassical tearing modes (NTM) triggering plasma disruptions. The Upper Launchers inject millimeter waves through a quasi-optical section consisting of three fixed and the front steering mirror set. The eight overlapping beams have focal points optimized for suppression of the q = 3/2 and q = 2/1 NTMs., Several project change requests required the redesign of the Upper Launchers and the connected ex-vessel system. This redesign includes a new boundary geometry of the launchers as well as a newly designed cooling system for the Blanket Shield Module (BSM), a modified flange of the BSM to the structural main frame and a refined optical design. Additionally shield blocks with integrated in-vessel waveguides were added and the closure plate with waveguide and supply line feedthroughs was adapted. Further changes, not all caused by PCRs, include newly designed ex-vessel waveguide components with a reduced aperture and redesigned ultra low-loss CVD diamond windows. Finally several components originally foreseen as off-the-shelf components have become part of the design scope. The new launcher design status is presented with selected results on numerical design validation.

The plasma diagnostic and control (D&C) system for a future tokamak demonstration fusion reactor (DEMO) will have to provide reliable operation near technical and physics limits, while its front-end components will be subject to strong adverse effects within the nuclear and high temperature plasma environment. The ongoing developments for the ITER D&C system represent an important starting point for progressing towards DEMO. Requirements for detailed exploration of physics are however pushing the ITER diagnostic design towards using sophisticated methods and aiming for large spatial coverage and high signal intensities, so that many front-end components have to be mounted in forward positions. In many cases this results in a rapid aging of diagnostic components, so that additional measures like protection shutters, plasma based mirror cleaning or modular approaches for frequent maintenance and exchange are being developed. Under the even stronger fluences of plasma particles, neutron/gamma and radiation loads on DEMO, durable and reliable signals for plasma control can only be obtained by selecting diagnostic methods with regard to their robustness, and retracting vulnerable front-end components into protected locations. Based on this approach, an initial DEMO D&C concept is presented, which covers all major control issues by signals to be derived from at least two different diagnostic methods (risk mitigation).

Objective To identify predictors of 10-year Expanded Disability Status Scale (EDSS) change after treatment initiation in patients with relapse-onset multiple sclerosis. Methods Using data obtained from MSBase, we defined baseline as the date of first injectable therapy initiation. Patients need only have remained on injectable therapy for 1 day and were monitored on any approved disease-modifying therapy, or no therapy thereafter. Median EDSS score changes over a 10-year period were determined. Predictors of EDSS change were then assessed using median quantile regression analysis. Sensitivity analyses were further performed. Results We identified 2,466 patients followed up for at least 10 years reporting post-baseline disability scores. Patients were treated an average 83% of their follow-up time. EDSS scores increased by a median 1 point (interquartile range = 0–2) at 10 years post-baseline. Annualized relapse rate was highly predictive of increases in median EDSS over 10 years (coeff = 1.14, p = 1.9 × 10−22). On-therapy relapses carried greater burden than off-therapy relapses. Cumulative treatment exposure was independently associated with lower EDSS at 10 years (coeff = −0.86, p = 1.3 × 10−9). Furthermore, pregnancies were also independently associated with lower EDSS scores over the 10-year observation period (coeff = −0.36, p = 0.009). Interpretation We provide evidence of long-term treatment benefit in a large registry cohort, and provide evidence of long-term protective effects of pregnancy against disability accrual. We demonstrate that high annualized relapse rate, particularly on-treatment relapse, is an indicator of poor prognosis. Ann Neurol 2016;80:89–100

In view of an efficient pulsed operation scenario of future nuclear fusion reactors, the effectiveness of a prompt and reliable plasma start-up is essential to improve plasma performance and reproducibility, especially after a disruptive event or to reduce dwell time between pulses. The foreseen solution to widen the operational window with respect to the pre-pulse conditions (background pressure and impurity content) is the use of Electron Cyclotron (EC) additional heating, which can compensate the radiation losses and sustain the plasma burn-trough phase. In order to design the operational scenario of future demonstrative reactors it is mandatory to set appropriate codes capable to extrapolate from present experiments the future scenarios. Experiments on TCV tokamak focused on discharge recovery by means of EC assisted start-up (82.7 GHz, XM2) have been carried out with toroidal electric field of 0.7 V/m, pressure before startup ranging between 2 and 10 mPa and neutral composition dominated by Ar impurity. Experimental results have been compared successfully with simulations provided by BKD0 code, which models in detail the burn-though phase and includes a consistent calculation of the EC absorbed power computed by the beam-tracing code GRAY in low density plasma and with a realistic description of the beam injection conditions, including polarization mix after beam reflection at the inner wall. The required additional power and impurity impact on startup has been determined for TCV and extrapolated to ITER, JT-60SA and DEMO. * See author list of 'S. Coda et al 2017 Nucl. Fusion 57 102011'

The development of the plasma diagnostic and control (D&C) system for a future tokamak demonstration fusion reactor (DEMO) is facing unprecedented challenges. The DEMO D&C system has to operate with very high reliability, since any loss of plasma control may result in machine damage. On the same time, high accuracy of the D&C system is needed in order to allow for plasma operation near operational limits, where the fusion power is maximized. The implementation and performance of diagnostic components is however limited by space restrictions (optimization of the tritium breeding rate; integrity of the first wall and divertor against loads), and by adverse effects acting on the front-end components (neutron and gamma radiation, heat loads, erosion and deposition). Finally, the capabilities of the available actuators (poloidal field coils, external heating and fueling) are limited as well. As part of the European DEMO conceptual design studies, the development of the D&C system has recently been launched [1]. A preliminary suite of candidate diagnostics for DEMO have been selected, aiming to cover all the main plasma control quantities with some redundancy, and choosing types and locations for diagnostic front-end components such that long-term durability with minimum need for maintenance can be expected under typical loads (e.g. neutron radiation, particle fluxes and fluencies). Specifically, only robust metallic or ceramics diagnostic components shall be used inside the vacuum vessel, while the more sensitive components shall be located at more remote (protected) positions. This initial plasma diagnostic suite comprises microwave diagnostics, magnetic coil based and Hall sensors, passive spectroscopy and radiation power measurements, divertor thermo-current measurement, infrared interferometry/polarimetry and neutron-gamma measurements. In the first R&D phase the possibilities and conditions for integration of diagnostic sightlines and front-end components into the machine have been investigated, and an understanding of the required number of channels and components has been obtained. The conditions for controllability of the DEMO plasma are being analyzed by numerical simulations. To this purpose, the transport modelling code ASTRA, coupled to a radiation module, has been connected to the Simulink simulation framework, and the performance properties of diagnostics and actuators are being added [2]. Similarly, the existing CREATE equilibrium code is being amended to include limitations of diagnostics and actuators, such that the controllability e.g. of fast VDEs can be simulated under DEMO relevant settings. Furthermore, predictive control oriented models such as RAPTOR are being further developed as an alternative approach to analyze the controllability of DEMO. The common goal is to arrive at numerical simulations which closely mimic the control of the DEMO plasma such that the controllability based on the available diagnostics and actuators can be demonstrated quantitatively. Based on these R&D results, an initial version of the DEMO diagnostic and control concept has been elaborated and will be presented in this paper.

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In the four-stage approach of the new ITER Research Plan, the first pre-fusion power operation (PFPO) phase will only have limited power available from external heating and current drive (H&CD) systems: 20-30 MW provided by the electron cyclotron resonance heating (ECRH) system. Accessing the H-mode confinement regime at such low auxiliary power requires operating at low magnetic field, plasma current and density, i.e. 1.8 T and 5 MA for a density between 40% and 50% of the Greenwald density. II-mode plasmas at 5 MA/1.8 T will also be investigated in the second PFPO phase when ITER will have its full complement of H&CD capabilities installed, i.e. 20-30 MW of ECRH, 20 MW of ion cyclotron resonance heating and 33 MW of neutral beam injection. This paper describes the operational constraints and the II&CD capabilities for such scenarios in hydrogen and helium plasmas, to assess their viability and the issues it will be possible to address with them. The modelling results show that 5 MA/1.8 T scenarios are viable and will allow the exploration of the H-mode physics and control issues foreseen in the ITER Research Programme in the PFPO phases.

The elements of high-frequency circuits, such as waveguide filters, are often subject to high temperatures due to power losses. Thermal expansion of the materials comprising the filter causes its deformation, which can significantly modify the S-parameters of the filter. In this work, the influence of thermal expansion on the properties of a waveguide filter is investigated. At first, the filter is heated up by about 100K. Then, a linear structural mechanics solver estimates the distribution of displacements within the system due to thermal expansion of its materials. Finally, sensitivity analysis with respect to this distribution of node displacements is performed. The results of sensitivity analysis are validated by their comparison with those obtained for a similar manual deformation of the system geometry. It is shown that the resulting scattering parameters are very similar in both cases, which confirms the reliability of the method. Moreover, the presented method does not require additional simulations for sensitivity estimation, which allows the analysis to be performed with no computational overhead.

BACKGROUND AND PURPOSE: Previous articles have demonstrated that carotid artery plaques may have enhancement after administration of contrast material. The purpose of this study was to evaluate the effect of enhancement in carotid artery classification. MATERIALS AND METHODS: Three hundred eighty consecutive patients (235 men, 145 women; median age 64, age range 32–87 years) were analyzed using a multidetector row CT scanner. Examinations were performed before and after CM administration. Carotid artery plaques with a attenuation value 130 HU were considered calcified. χ(2) tests, Student t tests, and Cohen analyses were performed. RESULTS: Before CM administration, we observed 226 calcified, 175 mixed, and 206 fatty plaques; after CM administration, 229 calcified, 213 mixed, and 165 fatty plaques were observed. A statistically significant difference between these 2 groups was observed (P = .016). We found that 19.9% of fatty plaques become mixed (n = 41), whereas 1.7% of the mixed plaques become calcified (n = 3). All calcified plaques remained in the same category. Fatty plaques that changed type showed a larger enhancement compared with those that remained in the same class (P = .001). Cohen analyses showed very good agreement between observers before (κ = 0.834) and after contrast material administration (κ = 0.86). CONCLUSIONS: The results of this study indicate that the carotid artery plaques (fatty and mixed) significantly change according to whether analysis is performed before or after administration of contrast material.

Non-invasive localization of premature ventricular beat (PVB) foci is very important for medical treatment of numerous cardiac diseases. In this work a model-based method of reconstruction of ectopic center locations is investigated. Within the scope of this method patient's multichannel ECG is used as a reference for optimization of an electrophysiological cardiac model. This model is based on the cellular automaton principle and utilizes anatomical data of the patient. Optimized are coordinates of the ectopic focus as well as excitation conduction velocity of ventricular myocardium. Initial values for these parameters are obtained by solving the linearized problem of electrocardiography in terms of activation times. Optimization is performed by minimization of discrepancy between the simulated and reference ECGs. The aim of the current work is to estimate the quality of ectopic focus localization delivered by this method. Four sample ectopic beats have been simulated, with their foci located in different regions of the left ventricle. 1% Gaussian noise has been introduced into the resulting ECGs. In this way the "measured" ECG signals for this investigation have been obtained. Afterwards the origin of each ectopic beat has been reconstructed using the model-based approach. The method has demonstrated reliable localization of PVB foci, reconstruction errors have not exceeded 6.1 mm.

Background: Retinopathy of prematurity (ROP) is a multifactorial disease, but little is known about its relationship with perinatal risk factors. We tested the hypothesis that the mode of delivery may be associated with threshold ROP as defined by CRYO-ROP. Methods: We conducted a prospective, cohort analysis of a database of all extremely low birth weight (ELBW) neonates (=birth weight