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.

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.

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.

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.

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.

(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.

Key Matrix Proteins Within the Pancreatic Islet Basement Membrane Are Differentially Digested During Human Islet Isolation.

Clinical islet transplantation achieves insulin independence in selected patients, yet current methods for extracting islets from their surrounding pancreatic matrix are suboptimal. The islet basement membrane (BM) influences islet function and survival and is a critical marker of islet integrity following rodent islet isolation. No studies have investigated the impact of islet isolation on BM integrity in human islets, which have a unique duplex structure. To address this, samples were taken from 27 clinical human islet isolations (donor age 41-59, BMI 26-38, cold ischemic time < 10 h). Collagen IV, pan-laminin, perlecan and laminin-α5 in the islet BM were significantly digested by enzyme treatment. In isolated islets, laminin-α5 (found in both layers of the duplex BM) and perlecan were lost entirely, with no restoration evident during culture. Collagen IV and pan-laminin were present in the disorganized BM of isolated islets, yet a significant reduction in pan-laminin was seen during the initial 24 h culture period. Islet cytotoxicity increased during culture. Therefore, the human islet BM is substantially disrupted during the islet isolation procedure. Islet function and survival may be compromised as a consequence of an incomplete islet BM, which has implications for islet survival and transplanted graft longevity.

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.

Meta-worry, worry, and anxiety in children and adolescents: relationships and interactions.

The metacognitive model has increased our understanding of the development and maintenance of generalized anxiety disorders in adults. It states that the combination of positive and negative beliefs about worry creates and sustains anxiety. A recent review argues that the model can be applied to children, but empirical support is lacking. The aim of the 2 presented studies was to explore the applicability of the model in a childhood sample. The first study employed a Danish community sample of youth (n = 587) ages 7 to 17 and investigated the relationship between metacognitions, worry and anxiety. Two multiple regression analyses were performed using worry and metacognitive processes as outcome variables. The second study sampled Danish children ages 7 to 12, and compared the metacognitions of children with a GAD diagnosis (n = 22) to children with a non-GAD anxiety diagnosis (n = 19) and nonanxious children (n = 14). In Study 1, metacognitive processes accounted for an additional 14% of the variance in worry, beyond age, gender, and anxiety, and an extra 11% of the variance in anxiety beyond age, gender, and worry. The Negative Beliefs about Worry scale emerged as the strongest predictor of worry and a stronger predictor of anxiety than the other metacognitive processes and age. In Study 2, children with GAD have significantly higher levels of deleterious metacognitions than anxious children without GAD and nonanxious children. The results offer partial support for the downward extension of the metacognitive model of generalized anxiety disorders to children.

Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection.

Dendritic cells (DCs) are key immune sentinels linking the innate and adaptive immune systems. DCs recognise danger signals and initiate T-cell tolerance, memory and polarisation. They are critical cells in responding to a viral illness. Obese individuals have been shown to have an impaired response to vaccinations against virally mediated conditions and to have an increased susceptibility to multi-organ failure in response to viral illness. We investigated if DCs are altered in an obese cohort (mean body mass index 51.7±7.3 kg m(-2)), ultimately resulting in differential T-cell responses. Circulating DCs were found to be significantly decreased in the obese compared with the lean cohort (0.82% vs 2.53%). Following Toll-like receptor stimulation, compared with lean controls, DCs generated from the obese cohort upregulated significantly less CD83 (40% vs 17% mean fluorescence intensity), a molecule implicated in the elicitation of T-cell responses, particularly viral responses. Obese DCs produced twofold more of the immunosuppressive cytokine interleukin (IL)-10 than lean controls, and in turn stimulated fourfold more IL-4-production from allogenic naive T cells. We conclude that obesity negatively impacts the ability of DCs to mature and elicit appropriate T-cell responses to a general stimulus. This may contribute to the increased susceptibility to viral infection observed in severe obesity.

Integrating genetic and imaging investigations into the clinical management of congenital hyperinsulinism.

Congenital Hyperinsulinism (CHI) is a rare but important cause of hypoglycaemia in infancy. CHI is a heterogeneous disease, but has a strong genetic basis; a number of genetic causes have been identified with CHI in about a third of individuals, chiefly in the genes that code for the ATP sensitive K(+) channels (KATP ) in the pancreatic ß-cells. Rapid KATP channel gene testing is a critical early step in the diagnostic algorithm of CHI, with paternal heterozygosity correlating with the occurrence of focal lesions. Imaging investigations to diagnose and localize solitary pancreatic foci have evolved over the last decade with (18)F-DOPA PET-CT scanning as the current diagnostic tool of choice. Although clinical management of CHI has improved significantly with the application of genetic screening and imaging investigations, much remains to be uncovered. This includes a better understanding of the molecular mechanisms for dysregulated insulin release in those patients without known genetic mutations, and the development of biomarkers that could characterize CHI, including long-term prognosis and targeted treatment planning, i.e. 'personalised medicine'. From the perspective of pancreatic imaging, it would be important to achieve greater specificity of diagnosis not only for focal lesions but also for diffuse and atypical forms of the disease.

A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene.

Usher syndrome type 1 describes the association of profound, congenital sensorineural deafness, vestibular hypofunction and childhood onset retinitis pigmentosa. It is an autosomal recessive condition and is subdivided on the basis of linkage analysis into types 1A through 1E. Usher type 1C maps to the region containing the genes ABCC8 and KCNJ11 (encoding components of ATP-sensitive K + (KATP) channels), which may be mutated in patients with hyperinsulinism. We identified three individuals from two consanguineous families with severe hyperinsulinism, profound congenital sensorineural deafness, enteropathy and renal tubular dysfunction. The molecular basis of the disorder is a homozygous 122-kb deletion of 11p14-15, which includes part of ABCC8 and overlaps with the locus for Usher syndrome type 1C and DFNB18. The centromeric boundary of this deletion includes part of a gene shown to be mutated in families with type 1C Usher syndrome, and is hence assigned the name USH1C. The pattern of expression of the USH1C protein is consistent with the clinical features exhibited by individuals with the contiguous gene deletion and with isolated Usher type 1C.

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.

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.

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.

Loss of functional KATP channels in pancreatic beta-cells causes persistent hyperinsulinemic hypoglycemia of infancy.

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a disorder of childhood associated with inappropriate hypersecretion of insulin by the pancreas. The pathogenesis of the condition has hitherto remained controversial. We show here that insulin-secreting cells from a homogeneous group of five infants with PHHI lack ATP-sensitive K+ channel (KATP) activity. As a consequence, PHHI beta-cells are spontaneously electrically active with high basal cytosolic Ca2+ concentrations due to Ca2+ influx. Our findings define the pathogenesis of this disease as a novel K+ channel disorder.

Emotional difficulties in seventh grade children in Denmark.

The present study investigates the prevalence of emotional difficulties and quality of life in a sample of 834 children from 56 seventh grade (aged 12-14 years) classes. Data was derived from a study of mental well-being developed by the National Council for Children, Denmark. The sample selection ensured that the children were nationally representative. Data was collected using the Strength and Difficulties Questionnaire (SDQ) and the Health Behaviour in School-aged Children (HBSC). Results indicated that 10.8% of children had concerns regarding emotional difficulties (6.6% definite concern; 4.2% some concern), and that significantly more girls than boys (44 girls and 10 boys) reported this concern. A novel finding was that emotional difficulties were related to children's perception of having low quality of life. Findings furthermore suggested that children's perception of a low home economy, less time spent on leisure activities, and female gender were all associated with emotional difficulties.

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.

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.

Observation of a velocity domain cooling instability in a radiative shock.

We report on experimental investigations into strong, laser-driven, radiative shocks in cluster media. Cylindrical shocks launched with several joules of deposited energy exhibit strong radiative effects including rapid deceleration, radiative preheat, and shell thinning. Using time-resolved propagation data from single-shot streaked Schlieren measurements, we have observed temporal modulations on the shock velocity, which we attribute to the thermal cooling instability, a process which is believed to occur in supernova remnants but until now has not been observed experimentally.