Active Control of Alfvén Eigenmodes by Externally Applied 3D Magnetic Perturbations.

The suppression and excitation of Alfvén eigenmodes have been experimentally obtained, for the first time, by means of externally applied 3D perturbative fields with different spatial spectra in a tokamak plasma. The applied perturbation causes an internal fast-ion redistribution that modifies the phase-space gradients responsible for driving the modes, determining, ultimately their existence. Hybrid kinetic-magnetohydrodynamic simulations reveal an edge resonant transport layer activated by the 3D perturbative field as the responsible mechanism for the fast-ion redistribution. The results presented here may help to control fast-ion driven Alfvénic instabilities in future burning plasmas with a significant fusion born alpha particle population.

Implementation of 26 Gy in five fractions over 1 week adjuvant radiotherapy for breast cancer: Prospective report of acute skin toxicity and consideration of resource implications.

PURPOSE: In March 2020, a 1-week adjuvant breast radiotherapy schedule, 26 Gy in 5 fractions, was adopted to reduce the risk of COVID19 for staff and patients. This study quantifies acute toxicity rates and the effect on linac capacity. MATERIALS AND METHODS: This is a report of consecutive patients receiving ultrafractionated breast radiotherapy ( ± sequential boost) Mar-Aug 2020. Virtual consultations assessed acute skin toxicity during treatment and weeks 1, 2, 3 and 4 post treatment using CTCAE V5 scoring criteria. The number of linac minutes saved was estimated accounting for boost and DIBH use. RESULTS: In total, 128/135 (95%) patients, including 31/33 boost patients, completed at least 3/5 assessments. 0/128 (0%) reported moist desquamation not confined to skin folds or minor bleeding (Grade 3), 41/128 (32%) reported brisk erythema, moist desquamation confined to skin folds or breast swelling (Grade 2), 62/128 (48%) reported faint erythema or dry desquamation (Grade 1) as their worst skin toxicity, with the remaining 20% reporting no skin toxicity. The highest prevalence of grade 2 toxicity occurred week 1 following treatment (20%), reducing to 3% by week 4. There was no difference in toxicity between those who received a boost versus not (p = 1.00). Delivering this schedule to 135 patients over six months saved 21,300 linac minutes and 1485 hospital visits compared to a 3-week schedule. CONCLUSION: Rapidly implementing ultrahypofractionated breast radiotherapy is feasible and acute toxicity rates are acceptable even when followed by boost.

Patient-Facing Clinical Decision Support for High Blood Pressure Control: Patient Survey.

BACKGROUND: High blood pressure (HBP) affects nearly half of adults in the United States and is a major factor in heart attacks, strokes, kidney disease, and other morbidities. To reduce risk, guidelines for HBP contain more than 70 recommendations, including many related to patient behaviors, such as home monitoring and lifestyle changes. Thus, the patient's role in controlling HBP is crucial. Patient-facing clinical decision support (CDS) tools may help patients adhere to evidence-based care, but customization is required. OBJECTIVE: Our objective was to understand how to adapt CDS to best engage patients in controlling HBP. METHODS: We conducted a mixed methods study with two phases: (1) survey-guided interviews with a limited cohort and (2) a nationwide web-based survey. Participation in each phase was limited to adults aged between 18 and 85 years who had been diagnosed with hypertension. The survey included general questions that assessed goal setting, treatment priorities, medication load, comorbid conditions, satisfaction with blood pressure (BP) management, and attitudes toward CDS, and also a series of questions regarding A/B preferences using paired information displays to assess perceived trustworthiness of potential CDS user interface options. RESULTS: We conducted 17 survey-guided interviews to gather patient needs from CDS, then analyzed results and created a second survey of 519 adults with clinically diagnosed HBP. A large majority of participants reported that BP control was a high priority (83%), had monitored BP at home (82%), and felt comfortable using technology (88%). Survey respondents found displays with more detailed recommendations more trustworthy (56%-77% of them preferred simpler displays), especially when incorporating social trust and priorities from providers and patients like them, but had no differences in action taken. CONCLUSIONS: Respondents to the survey felt that CDS capabilities could help them with HBP control. The more detailed design options for BP display and recommendations messaging were considered the most trustworthy yet did not differentiate perceived actions.

Quasicontinuous Exhaust Scenario for a Fusion Reactor: The Renaissance of Small Edge Localized Modes.

Tokamak operational regimes with small edge localized modes (ELMs) could be a solution to the problem of large transient heat loads in fusion reactors. A ballooning mode near the last closed flux surface governed by the pressure gradient and the magnetic shear there has been proposed for small ELMs. In this Letter, we experimentally investigate several stabilizing effects near the last closed flux surface and present linear ideal simulations that indeed develop ballooninglike fluctuations there and connect them with nonlinear resistive simulations. The dimensionless parameters of the small ELM regime in the region of interest are very similar to those in a reactor, making this regime the ideal exhaust scenario for a future device.

Provider Perspectives on Patient- and Provider-Facing High Blood Pressure Clinical Decision Support.

BACKGROUND: Hypertension, persistent high blood pressures (HBP) leading to chronic physiologic changes, is a common condition that is a major predictor of heart attacks, strokes, and other conditions. Despite strong evidence, care teams and patients are inconsistently adherent to HBP guideline recommendations. Patient-facing clinical decision support (CDS) could help improve recommendation adherence but must also be acceptable to clinicians and patients. OBJECTIVE: This study aimed to partly address the challenge of developing a patient-facing CDS application, we sought to understand provider variations and rationales related to HBP guideline recommendations and perceptions regarding patient role and use of digital tools. METHODS: We engaged hypertension experts and primary care respondents to iteratively develop and implement a pilot survey and a final survey which presented five clinical cases that queried clinicians' attitudes related to actions; variations; prioritization; patient input; importance; and barriers for HBP diagnosis, monitoring, and treatment. Analysis of Likert's scale scores was descriptive with content analysis for free-text answers. RESULTS: Fifteen hypertension experts and 14 providers took the pilot and final version of the surveys, respectively. The majority (>80%) of providers felt the recommendations were important, yet found them difficult to follow-up to 90% of the time. Perceptions of relative amounts of patient input and patient work for effective HBP management ranged from 22 to 100%. Stated reasons for variation included adverse effects of treatment, patient comorbidities, shared decision-making, and health care cost and access issues. Providers were generally positive toward patient use of electronic CDS applications but worried about access to health care, nuance of recommendations, and patient understanding of the tools. CONCLUSION: At baseline, provider management of HBP is heterogeneous. Providers were accepting of patient-facing CDS but reported preferences for that CDS to capture the complexity and nuance of guideline recommendations.

Association Between Ex Vivo Human Ulcerative Colitis Explant Protein Secretion Profiles and Disease Behaviour.

BACKGROUND: The clinical course of ulcerative colitis (UC) is variable. There is an unmet clinical need for biomarkers of UC disease behaviour. We aimed to evaluate the association between ex vivo human UC explant conditioned media (explant-CM) secreted protein profiles and UC disease behaviour. METHODS: UC patients undergoing endoscopy were prospectively recruited. Endoscopic biopsies were collected and explant-CM generated. Association between explant-CM protein secretion profiles and disease progression was evaluated. Disease progression was defined as the requirement for corticosteroid therapy, UC-related hospitalisation, UC-related surgery or the introduction of a new immunomodulatory agent. Association between explant-CM secreted protein profiles and anti-TNF failure status was also evaluated. p values < 0.05 were considered significant in analyses. RESULTS: Twenty-four UC patients were included (age [median, range]) 55 [21-72] years; 50% female. Disease progression during follow-up occurred in twelve (50%) patients. Multivariate analysis, including endoscopic remission status, demonstrated reduced IL-2 secretion to be independently associated with UC disease progression, p = 0.01. In univariate analysis, anti-TNF failure status was associated with significantly increased IL-17A/F (p = 0.015) and IL-12 / IL-23p40 (p = 0.044) concentrations. In multivariate analysis, there was a trend towards an association between IL-17A/F and anti-TNF failure status (p = 0.069); FLT-1 was demonstrated to be independently associated with anti-TNF failure status (p = 0.016). CONCLUSION: Reduced explant-CM secreted IL-2 is associated with UC disease progression. Increased secretion of IL-23 pathway-associated cytokines was observed in anti-TNF failure status consistent with previous reports. Ex vivo human UC explants, generated from endoscopic biopsies, have potential as precision medicine tools in inflammatory bowel disease.

Late Toxicity and Long-Term Local Control in Patients With Ultra-Central Lung Tumours Treated by Intensity-Modulated Radiotherapy-Based Stereotactic Ablative Body Radiotherapy With Homogenous Dose Prescription.

AIMS: To report late toxicity and long-term outcomes of intensity-modulated radiotherapy (IMRT)-based stereotactic ablative body radiotherapy (SABR) in patients with ultra-central lung tumours. MATERIALS AND METHODS: This is a single-institution retrospective analysis of patients treated with SABR for ultra-central tumours between May 2008 and April 2016. Ultra-central location was defined as tumour (GTV) abutting or involving trachea, main or lobar bronchi. Respiratory motion management and static-field dynamic-IMRT were used, with dose prescribed homogeneously (maximum <120%). Descriptive analysis, Kaplan-Meier method, log-rank test and Cox regression were used to assess outcomes. RESULTS: Sixty-five per cent of patients had inoperable primary non-small cell lung cancer and 35% had lung oligometastases. The median age was 72 (range 34-85) years. The median gross tumour volume and planning target volume (PTV) were 19.6 (range 1.7-203.3) cm3 and 57.4 (range 7.7-426.6) cm3, respectively. The most commonly used dose fractionation was 60 Gy in eight fractions (n = 51, 87.8%). Median BED10 for D98%PTV and D2%PTV were 102.6 Gy and 115.06 Gy, respectively. With a median follow-up of 26.5 (range 3.2-100.5) months, fatal haemoptysis occurred in five patients (8.7%), of which two were directly attributable to SABR. A statistically significant difference was identified between median BED3 for 4 cm3 of airway, for patients who developed haemoptysis versus those who did not (147.4 versus 47.2 Gy, P = 0.005). At the last known follow-up, 50 patients (87.7%) were without local recurrence. Freedom from local progression at 2 and 4 years was 92 and 79.8%, respectively. The median overall survival was 34.3 (95% confidence interval 6.1-61.6) months. Overall survival at 2 and 4 years was 55.1 and 41.2%, respectively. CONCLUSION: In patients with high-risk ultra-central lung tumours, IMRT-based SABR with homogenous dose prescription achieves high local control, similar to that reported for peripheral tumours. Although fatal haemoptysis occurred in 8.7% of patients, a direct causality with SABR was evident in only 3%. Larger studies are warranted to ascertain factors associated with outcomes, especially toxicity, and identify patients who would probably benefit from this treatment.

Stereotactic Ablative Radiation Therapy for Large (≥5 cm) Non-small Cell Lung Carcinoma.

AIMS: Stereotactic ablative radiation therapy (SABR) is a standard of care for medically inoperable early stage non-small cell lung carcinoma. Tumours greater than 5 cm have been excluded from randomised trials using SABR and, hence, it is not used as a standard for larger lung tumours. However, improvements in radiation therapy techniques and the success of SABR in treatment of early stage disease may allow safe delivery of ablative doses to larger tumours. We analysed our experience with tumours ≥5 cm to determine the efficacy and toxicity profile of SABR in this setting. MATERIALS AND METHODS: We evaluated survival, control rates, patterns of failure and toxicity in patients with a tumour diameter larger than 5 cm that had no nodal or distant metastases treated with SABR technology. Patients had been treated in two centres since 2009 and were retrospectively analysed. All patients had positron emission tomography staging, were discussed at a tumour board and were documented to have no nodal or distant metastatic disease. Treatment outcomes were analysed using Kaplan-Meier estimates and compared using the Log-rank test. Cox regression was used to investigate the association between the survival outcomes and predictor variables. RESULTS: In total, 86 patients were identified. Six patients had no follow-up imaging. Therefore, 80 patients were available for analysis. All patients were reclassified according to the updated AJCC eighth edition. The median follow-up was 19.6 months. No patients received neoadjuvant or concurrent systemic therapy. One patient received adjuvant systemic therapy. The median age at treatment was 77 years (range 58-91). Eighty-four per cent were stage T3N0M0 and 16% were staged T4N0M0. The median tumour diameter was 5.8 cm (range 5.0-9.3 cm). The median gross tumour volume, measured on a single phase of the respiratory cycle, was 45.7 cm3 (range 12.1-203.3 cm3). The median overall survival was 20.9 months (95% confidence interval 12.6-29.1 months). One-, 2- and 3-year overall survival was 71%, 48% and 32%, respectively. The median local failure-free survival was 19.5 months (95% confidence interval 14.4-24.6). The median disease-free survival was 15.1 months (95% confidence interval 9.9-20.4 months). Local control at 1, 2 and 3 years was 85% (95% confidence interval 76-94%), 71% (95% confidence interval 58-84%) and 57% (95% confidence interval 40-74%), respectively. Forty-four patients (55%) had any treatment failure (local, mediastinal, intrapulmonary or distant metastases). Out-of-field intrapulmonary disease progression was the most common mode of failure, occurring in 21 patients (26%). Local failure occurred in 19 patients (24%) - alone or in combination with other progression. Distant metastases occurred in 20 patients (25%). Neither histological subtype, tumour size nor gross tumour volume had a statistically significant effect on local failure-free survival. Two patients experienced grade 3 late dyspnoea. There were no other reported grade 3 or higher acute or late toxicities. CONCLUSION: SABR for larger lung tumours ≥5 cm results in high local control and acceptable survival in patients with medically inoperable large non-small cell lung carcinoma treated with radiation alone. Such patients should be considered for SABR owing to fewer treatment fractions and acceptable toxicity. Local control analysis reveals a sustained pattern of local failure emphasising the need for long-term follow-up. Improvements in technical strategies are required to further improve local control.

Recommendations for improving national clinical datasets for health equity research.

Health and healthcare disparities continue despite clinical, research, and policy efforts. Large clinical datasets may not contain data relevant to healthcare disparities and leveraging these for research may be crucial to improve health equity. The Health Disparities Collaborative Research Group was commissioned by the Patient-Centered Outcomes Research Institute to examine the data science needs for quality and complete data and provide recommendations for improving data science around health disparities. The group convened content experts, researchers, clinicians, and patients to produce these recommendations and suggestions for implementation. Our desire was to produce recommendations to improve the usability of healthcare datasets for health equity research. The recommendations are summarized in 3 primary domains: patient voice, accurate variables, and data linkage. The implementation of these recommendations in national datasets has the potential to accelerate health disparities research and promote efforts to reduce health inequities.

Adverse childhood experiences: association with physical and mental health conditions among older adults in Bhutan.

OBJECTIVES: Adverse childhood experiences (ACEs) are events stressful, traumatic, and related to the development of a wide range of health conditions throughout the person's lifespan. This study explored the relationship between ACEs and health conditions among older adults in Bhutan. STUDY DESIGN: Cross-sectional survey. METHODS: Older adults aged 60-101 years (n = 337) completed a face-to-face interview in a convenient community setting in the four major towns of Bhutan. Measurements included the modified World Health Organization Adverse Childhood Experiences International Questionnaire and the checklist of chronic health conditions. RESULTS: Commonest ACEs reported by the sample were related to the contribution of physical labour in childhood (n = 284 [84.3%]) and witnessing of community violence (n = 185 [54.9%]). Assuming an adult role while still a child highly co-occur with other forms of ACEs. Compared to 0-2 ACEs, participants with ≥7 ACEs had the higher odds of reporting lung disease (odds ratio [OR] = 2.15, 95% confidence interval [CI]: 1.03-4.49), visual impairment (OR = 2.38, 95%CI: 1.16-4.85), insomnia (OR = 2.35, 95%CI: 1.11-4.98), and memory decline (OR = 2.30, 95%CI: 1.10-4.78) by twofold and high blood pressure by threefold (OR = 3.21, 95%CI: 1.39-7.38). Overall, the odds of self-rated poor health conditions among those ≥7 ACEs compared to 0-2 ACEs was high by almost twofold (OR = 1.97; 95%CI: 1.04-3.73). CONCLUSIONS: The influence of ACEs on health conditions persisted into late adulthood, and older people in Bhutan have had a complex variety of chronic health conditions implicating greater demand on the free healthcare system in Bhutan. ACEs prevention is critical to promote better health for a country like Bhutan, where the healthcare services are provided free of cost to its citizens.

Enhanced angiogenic function in response to fibroblasts from psoriatic arthritis synovium compared to rheumatoid arthritis.

INTRODUCTION: Angiogenesis is an early event in the pathogenesis of both psoriatic arthritis (PsA) and rheumatoid arthritis (RA); however, there are striking differences in blood vessel morphology and activation between the two arthropathies. The aim of this study was to assess if the PsA and RA joint microenvironments differentially regulate endothelial cell function. METHODS: PsA and RA primary synovial fibroblasts (SFC) were isolated from synovial biopsies, grown to confluence, and supernatants harvested and termed 'conditioned media' (CM). Human umbilical vein endothelial cells (HUVEC) were cultured with PsA SFC or RA SFC-CM (20%). HUVEC tube formation, migration, and PBMC adhesion were assessed by matrigel tube formation, wound repair, and PBMC adhesion assays. HUVEC cell surface expression of ICAM, VCAM, and E-Selectin was assessed by flow cytometry. Transcriptome analysis of genes promoting angiogenesis was performed by real-time PCR. Finally, a MSD multiplex angiogenic assay was performed on PsA SFC and RA SFC supernatants. RESULTS: Macroscopic synovitis and vascularity were similar in PsA and RA patients; however, significant differences in vascular morphological pattern were recorded with tortuous, elongated vessels observed in PsA compared to straight regular branching vessels observed in RA. Transcriptome analysis showed strong upregulation of the pro-angiogenic signature in HUVEC primed with PsA SFC-CM compared to RA SFC-CM and basal control. In parallel, paired PsA SFC-CM significantly induced HUVEC tube formation compared to that of RA SFC-CM. Furthermore, PsA SFC-CM induced HUVEC migration was paralleled by a significant induction in VEGFA, PFKFB3, ICAM-1, and MMP3 mRNA expression. A significant increase in PBMC adhesion and cell surface expression of VCAM-1, ICAM-1, and E-Selectin expression was also demonstrated in PsA SFC-CM-primed HUVEC compared to RA SFC-CM. Finally, VEGF, TSLP, Flt-1, and Tie-2 expression was elevated in PsA SFC-CM compared to RA SFC-CM, with no significant difference in other pro-angiogenic mediators including MIP-3, bFGF, PIGF, and MCP-1. CONCLUSION: PsA SFC and RA SFC secreted factors differentially regulate endothelial cell function, with soluble mediators in the PsA joint microenvironment inducing a more pro-angiogenic phenotype compared to the RA.

Therapies and outcomes of congenital hyperinsulinism-induced hypoglycaemia.

Congenital hyperinsulinism is a rare disease, but is the most frequent cause of persistent and severe hypoglycaemia in early childhood. Hypoglycaemia caused by excessive and dysregulated insulin secretion (hyperinsulinism) from disordered pancreatic ß cells can often lead to irreversible brain damage with lifelong neurodisability. Although congenital hyperinsulinism has a genetic cause in a significant proportion (40%) of children, often being the result of mutations in the genes encoding the KATP channel (ABCC8 and KCNJ11), not all children have severe and persistent forms of the disease. In approximately half of those without a genetic mutation, hyperinsulinism may resolve, although timescales are unpredictable. From a histopathology perspective, congenital hyperinsulinism is broadly grouped into diffuse and focal forms, with surgical lesionectomy being the preferred choice of treatment in the latter. In contrast, in diffuse congenital hyperinsulinism, medical treatment is the best option if conservative management is safe and effective. In such cases, children receiving treatment with drugs, such as diazoxide and octreotide, should be monitored for side effects and for signs of reduction in disease severity. If hypoglycaemia is not safely managed by medical therapy, subtotal pancreatectomy may be required; however, persistent hypoglycaemia may continue after surgery and diabetes is an inevitable consequence in later life. It is important to recognize the negative cognitive impact of early-life hypoglycaemia which affects half of all children with congenital hyperinsulinism. Treatment options should be individualized to the child/young person with congenital hyperinsulinism, with full discussion regarding efficacy, side effects, outcomes and later life impact.

Observations of core ion cyclotron emission on ASDEX Upgrade tokamak.

The B-dot probe diagnostic suite on the ASDEX Upgrade tokamak has recently been upgraded with a new 125 MHz, 14 bit resolution digitizer to study ion cyclotron emission (ICE). While classic edge emission from the low field side plasma is often observed, we also measure waves originating from the core with fast fusion protons or beam injected deuterons being a possible emission driver. Comparing the measured frequency values with ion cyclotron harmonics present in the plasma places the origin of this emission on the magnetic axis, with the fundamental hydrogen/second deuterium cyclotron harmonic matching the observed values. The actual values range from ∼27 MHz at the on-axis toroidal field BT = -1.79 T to ∼40 MHz at BT = -2.62 T. When the magnetic axis position evolves during this emission, the measured frequency values track the changes in the estimated on-axis cyclotron frequency values. Core ICE is usually a transient event lasting ∼100 ms during the neutral beam startup phase. However, in some cases, core emission occurs in steady-state plasmas and lasts for longer than 1 s. These observations suggest an attractive possibility of using a non-perturbing ICE-based diagnostic to passively monitor fusion alpha particles at the location of their birth in the plasma core, in deuterium-tritium burning devices such as ITER and DEMO.

Application of Bayes' to the prediction of referral decisions made by specialist optometrists in relation to chronic open angle glaucoma.

PURPOSE: To determine the accuracy of a Bayesian learning scheme (Bayes') applied to the prediction of clinical decisions made by specialist optometrists in relation to the referral refinement of chronic open angle glaucoma. METHODS: This cross-sectional observational study involved collection of data from the worst affected or right eyes of a consecutive sample of cases (n = 1,006) referred into the West Kent Clinical Commissioning Group Community Ophthalmology Team (COT) by high street optometrists. Multilevel classification of each case was based on race, sex, age, family history of chronic open angle glaucoma, reason for referral, Goldmann Applanation Tonometry (intraocular pressure and interocular asymmetry), optic nerve head assessment (vertical size, cup disc ratio and interocular asymmetry), central corneal thickness and visual field analysis (Hodapp-Parrish-Anderson classification). Randomised stratified tenfold cross-validation was applied to determine the accuracy of Bayes' by comparing its output to the clinical decisions of three COT specialist optometrists; namely, the decision to discharge, follow-up or refer each case. RESULTS: Outcomes of cross-validation, expressed as means and standard deviations, showed that the accuracy of Bayes' was high (95%, 2.0%) but that it falsely discharged (3.4%, 1.6%) or referred (3.1%, 1.5%) some cases. CONCLUSIONS: The results indicate that Bayes' has the potential to augment the decisions of specialist optometrists.

(ICORG 05-03): prospective randomized non-inferiority phase III trial comparing two radiation schedules in malignant spinal cord compression (not proceeding with surgical decompression); the quality of life analysis.

BACKGROUND: The optimal primary external beam radiation therapy (EBRT) radiation schedule for malignant epidural spinal cord compression (MSCC) remains to be determined. The ICORG 05-03 trial assessed if a 10 Gy single fraction radiation schedule was not inferior to one with 20 Gray (Gy) in five daily fractions, in terms of functional motor outcome, for the treatment of MSCC in patients not proceeding with surgical decompression. This article reports on two of the secondary endpoints, Quality of life (QoL), assessed according to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) version 3.0 (EORTC Data Center, Brussels, Belgium) and pain control assessed using a visual analog scale. METHODS: A randomized, parallel group, multicenter phase III trial was conducted by Cancer Trials Ireland (formerly All-Ireland Cooperative Oncology Research Group, ICORG), across five hospital sites in Ireland and Northern Ireland. Patients were randomized to 10 Gy single fraction of EBRT or 20 Gy in five fractions in a 1:1 ratio. Patients with baseline and 5-week follow up QoL data are included in this analysis. FINDINGS: From 2006 to 2014, 112 eligible patients were enrolled for whom 57 were evaluated for this secondary analysis. After adjusting for pre-intervention scores, there was no statistically significant difference in post-treatment Summary scores (excl. FI and QL), or pain scores between the two RT schedules at 5 weeks and 3 months following EBRT. There was a statistically significant relationship between the pretreatment and post-treatment Summary scores (p = .002) but not between the pre-treatment and post-treatment pain scores. INTERPRETATION: Primary radiotherapy for the treatment of MSCC significantly improves QoL in patients not proceeding with surgical decompression. After adjusting for pre-intervention scores, there was no statistically significant difference between a 10 Gy single fraction radiation schedule and one with 20 Gy in five daily fractions on post-treatment QoL Summary scores. For most patients, an effective treatment with low burden would be desirable. A single fraction schedule should be considered for this group of patients.

A Phase II Toxicity End Point Trial (ICORG 99-09) of Accelerated Dose-escalated Hypofractionated Radiation in Non-small Cell Lung Cancer.

AIMS: The objective of this phase II clinical trial was to prospectively evaluate the safety and efficacy of accelerated hypofractionated three-dimensional conformal radiation therapy (3DCRT) in localised non-resectable/non-operable non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Sixty patients with stage I-III NSCLC were enrolled in a prospective single-arm All Ireland Co-operative Oncology Research Group (ICORG 99-09) toxicity end point phase II trial. The protocol allocated patients between three radiation schedule dose levels (60, 66 or 72 Gy, in 20, 22 and 24 fractions, respectively, 3 Gy daily, five fractions per week) according to combined lung V25Gy (V25Gy ≤ 30%) with built-in early stopping toxicity rules. The primary end point was toxicity with evaluation of dose-limiting toxicity. The secondary objectives included radiological tumour response rate at 3 months after the completion of radiation therapy and the thoracic progression-free survival time. RESULTS: Sixty patients were recruited from August 1999 to June 2009. Forty-nine patients were included in the primary per-protocol analysis. Eleven patients were not evaluable. In the first 30 evaluable patient cohort, severe oesophageal toxicity was reported in two patients (2/49; 4% experiencing grade 5 oesophageal late toxicity, related to the 97% oesophageal length). The trial was temporarily closed and was then reopened to validate an oesophageal dose volume constraint (DVC) of limiting the length of oesophagus fully encompassed by the 97% isodose to less than 1 cm (applied to 21 patients). The trial prospectively showed the safety of the oesophageal DVC, with no oesophageal toxicity above grade 3 thereafter. Thirty-nine per cent of patients had disease progression at 3-4 months after radiotherapy, 22% had stable disease, 20% had a complete response and 14% had a partial response. The median overall survival was 13.6 months (95% confidence interval 10.5-16.7) and overall survival at 1 and 3 years was 57% and 29%, respectively. CONCLUSION: A strategy using accelerated hypofractionated 3DCRT is feasible and reasonably safe for patients with inoperable NSCLC. It is safe to deliver for centrally located tumours if DVCs are applied to the oesophagus, which is the primary dose-limiting toxicity. Further studies are required to assess the efficacy of hypofractionated regimens for centrally located tumours using an oesophageal DVC and monitoring for oesophageal toxicity.

Influence of non-local thermodynamic equilibrium and Zeeman effects on magnetic equilibrium reconstruction using spectral motional Stark effect diagnostic.

The Motional Stark Effect (MSE) diagnostic is a well established technique to infer the local internal magnetic field in fusion plasmas. In this paper, the existing forward model which describes the MSE data is extended by the Zeeman effect, fine-structure, and relativistic corrections in the interpretation of the MSE spectra for different experimental conditions at the tokamak ASDEX Upgrade. The contribution of the non-Local Thermodynamic Equilibrium (non-LTE) populations among the magnetic sub-levels and the Zeeman effect on the derived plasma parameters is different. The obtained pitch angle is changed by 3°…4° and by 0.5°…1° including the non-LTE and the Zeeman effects into the standard statistical MSE model. The total correction is about 4°. Moreover, the variation of the magnetic field strength is significantly changed by 2.2% due to the Zeeman effect only. While the data on the derived pitch angle still could not be tested against the other diagnostics, the results from an equilibrium reconstruction solver confirm the obtained values for magnetic field strength.

Field-Line Localized Destabilization of Ballooning Modes in Three-Dimensional Tokamaks.

Field-line localized ballooning modes have been observed at the edge of high confinement mode plasmas in ASDEX Upgrade with rotating 3D perturbations induced by an externally applied n=2 error field and during a moderate level of edge localized mode mitigation. The observed ballooning modes are localized to the field lines which experience one of the two zero crossings of the radial flux surface displacement during one rotation period. The localization of the ballooning modes agrees very well with the localization of the largest growth rates from infinite-n ideal ballooning stability calculations using a realistic 3D ideal magnetohydrodynamic equilibrium. This analysis predicts a lower stability with respect to the axisymmetric case. The primary mechanism for the local lower stability is the 3D distortion of the local magnetic shear.

Interviews with Patients and Providers on Transgender and Gender Nonconforming Health Data Collection in the Electronic Health Record.

Purpose: Meaningful use (MU) and Uniform Data Systems (UDSs) are calling for the collection of gender identity (GI) in electronic health record (EHR) systems; however, many transgender and nonconforming (TGNC) patients may not feel safe disclosing their GI and the data collection is not designed to guide care provision. This study explores the complexities surrounding the inclusion of GI in EHR data collection and how it can best serve patients and providers. Methods: Using a semistructured interview format, TGNC patients (n=7) and providers (n=5) who care for TGNC patients were asked about data collection procedures and the use of these data within community health centers in Oregon. Using a constant comparative data analysis methodology, interview transcripts were coded for emergent concepts until overlapping themes were identified. Results: Both patients and providers expressed a need for the EHR to expand upon MU and UDS-recommended fields to include current pronouns and name and gender identifiers in a forward-facing display to prevent misgendering by clinic staff and providers. Furthermore, they both cited the need for a broader range of birth-assigned sex and gender options. TGNC patients and providers disagreed on the scope of health information to be collected as well as who should be tasked with the data collection. Conclusion: These interviews offer us a glimpse into the structural difficulties of creating an EHR system that serves the needs of clinicians while providing safe and culturally competent care to TGNC patients.