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A prototype 1-d silicon strip detector system for applications in autoradiography is described. The commercially available detector allows 2-d imaging to be achieved by acquiring projection data at multiple angles as the source is rotated above the detector. Standard image reconstruction techniques are employed to produce the final 2-d image. The first test performed is presented showing that tomography is possible with 1-d silicon strip detectors.

Maximum standardized uptake value (SUVmax) from fluorodeoxyglucose (FDG) positron emission tomography (PET) scans is a semi quantitative measure that is increasingly used in the clinical practice for diagnostic and therapeutic response assessment purposes. Technological advances such as the implementation of the point spread function (PSF) in the reconstruction algorithm have led to higher signal to noise ratio and increased spatial resolution. The impact on SUVmax measurements has not been studied in clinical setting. We studied the impact of PSF on SUVmax in 30 consecutive lung cancer patients. SUVmax values were measured on PET-computed tomography (CT) scans reconstructed iteratively with and without PSF (respectively high-definition [HD] and non-HD). HD SUVmax values were significantly higher than non-HD SUVmax. There was excellent correlation between HD and non-HD values. Details of reconstruction and PSF implementation in particular have important consequences on SUV values. Nuclear Medicine physicians and radiologists should be aware of the reconstruction parameters of PET-CT scans when they report or rely on SUV measurements. [ABSTRACT FROM AUTHOR]

In this study the authors speculate about hypothetical effective-dose (E) reduction through limiting post-chemotherapy PET–CT scanning to lymphoma sites previously identified on pre-treatment CT. E reductions/scan time savings are compared between post-treatment standard and theoretically limited PET–CT scans. The influence of patient age with E savings and associated clinical implication for 100 subjects are discussed. The greatest E theoretical savings of 52 and 32 % for the CT contribution and combined PET–CT, respectively, were seen in patients <18 y old using limited scans in this study, with a potential mean time saving of 16 min per patient across the entire cohort. However, the limited PET–CT regime here missed a 1 % rate of unexpected cancer that standard PET–CT recorded. The authors recommend performing larger scale multi-centre studies comparing PET–CT pre- and post-chemotherapy to establish full clinical efficacy of this method. [ABSTRACT FROM PUBLISHER]

The aim was to evaluate the feasibility of fractal analysis for assessing the spatial pattern of colorectal tumour perfusion at dynamic contrast-enhanced CT (perfusion CT). Twenty patients with colorectal adenocarcinoma underwent a 65-s perfusion CT study from which a perfusion parametric map was generated using validated commercial software. The tumour was identified by an experienced radiologist, segmented via thresholding and fractal analysis applied using in-house software: fractal dimension, abundance and lacunarity were assessed for the entire outlined tumour and for selected representative areas within the tumour of low and high perfusion. Comparison was made with ten patients with normal colons, processed in a similar manner, using two-way mixed analysis of variance with statistical significance at the 5% level. Fractal values were higher in cancer than normal colon (p < or = 0.001): mean (SD) 1.71 (0.07) versus 1.61 (0.07) for fractal dimension and 7.82 (0.62) and 6.89 (0.47) for fractal abundance. Fractal values were lower in 'high' than 'low' perfusion areas. Lacunarity curves were shifted to the right for cancer compared with normal colon. In conclusion, colorectal cancer mapped by perfusion CT demonstrates fractal properties. Fractal analysis is feasible, potentially providing a quantitative measure of the spatial pattern of tumour perfusion. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To report nutrient intakes for three different ethnic groups living in inner city Manchester and explore under-reporting in each group. DESIGN: Cross-sectional survey. All participants completed one of three food frequency questionnaires, specifically developed for each ethnic group, and took part in a larger international survey of risk factors for diabetes and hypertension. SETTING: Participants were drawn randomly from seven GP registers in inner city Manchester, UK. PARTICIPANTS: Men and women aged 25-79 years, 86 European, 246 African-Caribbean origin and 84 Pakistani origin participants were included in the analysis. RESULTS: Body mass index was highest in the Pakistani women, 30.2 kg m-2. European participants had the highest reported energy intakes (EIs) for men and women (10.9 and 9.6 MJ, respectively). Pakistani men and women had the highest percentage of energy from fat (36.7 and 36.6%, respectively). Iron intakes were low in the African-Caribbean group and calcium intakes were low in the Pakistani group. Under-reporting [assessed as EI : basal metabolic rate (BMR) ratio <1.2] appeared to be high and occurred across all ethnic groups, with those apparently under-reporting having higher BMIs in all groups. CONCLUSION: The data provide nutrient intake estimates in three different ethnic groups using a similar method. Limitations include under-reporting across all ethnic groups in a similar pattern with under-reporters having higher BMIs in all groups, as found elsewhere. [ABSTRACT FROM AUTHOR]

We report methods for (a) transforming a three-dimensional geometry acquired by magnetic resonance angiography (MRA) in vivo, or by imaging a model cast, into a computational surface representation, (b) use of this to construct a three dimensional numerical grid for computational fluid dynamic (CFD) studies, and (c) use of the surface representation to produce a stereo-lithographic replica of the real detailed geometry, at a scale convenient for detailed magnetic resonance imaging (MRI) flow studies. This is applied to assess the local flow field in realistic geometry arterial bypass grafts. Results from a parallel numerical simulation and MRI measurement of flow in an aorto-coronary bypass graft with various inlet flow conditions demonstrate the strong influence of the graft inlet waveform on the perianastomotic flow field. A sinusoidal and a multi harmonic coronary flow waveform both with a mean Reynolds number (Re) of 100 and a Womersley parameter of 2.7 were applied at the graft inlet. A weak axial flow separation region just distal to the toe was found in sinusoidal flow near end deceleration (Re = 25). At the same location and approximately the same point in the cycle (Re = 30) but in coronary flow, the axial flow separation was stronger and more spatially pronounced. No axial flow separation occurred in steady flow for Re = 100. Numerical predictions indicate a region in the vicinity of the suture line (where there is a local narrowing of the graft) with a wall shear magnitude in excess of five times that associated with fully developed flow at the graft inlet. [ABSTRACT FROM AUTHOR]

Abstract: Aims: This study investigated an adaptive threshold-based method to delineate the target volume using 18fluoro-2-deoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT) before and during a course of radical radiotherapy or chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck. Materials and methods: Ten patients were enrolled between March 2006 and May 2008. 18FDG PET/CT scans were carried out 72h before the start of radiotherapy and then at three time points during radiotherapy (8–18, 36–50 and 66Gy). Functional volumes were delineated using an adaptive iterative algorithm weighted according to the mean standard uptake value (SUVmean) within the region of interest. The background 18FDG uptake, maximum standard uptake value (SUVmax) and SUVmean within the volumes were assessed. Results: There was no significant reduction in the primary target volumes defined by the adaptive threshold during radiotherapy. However, the SUVmax significantly reduced within the primary (P =0.003–0.011) and lymph node (P <0.0001) target volume at 36–50 and 36–66Gy compared with 0Gy. The SUVmean was negatively correlated to radiation dose (P <0.0001–0.014). The ratio between the background uptake of 18FDG and the SUVmean significantly reduced for both the lymph node target volume at 36–50Gy and the primary volume at 66Gy. The lack of significant correlation between the defined volume and radiation dose was because the SUVmean within the region of interest used to define the edge of the volume was equal to or less than the background 18FDG uptake and the software was unable to effectively differentiate between tumour and background uptake. Conclusions: The adaptive threshold method may be of benefit when used to define the target volume before the start of radiotherapy. This method was not beneficial during radiotherapy because the software is not sensitive enough to distinguish tumour from background and define a volume. 18FDG PET/CT-guided volumes delineated by automatic adaptive thresholding methods should only be used for dose escalation with the pretreatment imaging. [Copyright &y& Elsevier]

Objective: Chest pain (CP) is key in diagnosing myocardial infarction (MI). Patients with diabetes mellitus (DM) are at increased risk of an MI but may experience less CP, leading to delayed treatment and worse outcomes. We compared the prevalence of CP in those with and without DM who had an MI., Methods: The study population was people with MI presenting to healthcare services. The outcome measure was the absence of CP during MI, comparing those with and without DM. Medline and Embase databases were searched to 18 October 2021, identifying 9272 records. After initial independent screening, 87 reports were assessed for eligibility against the inclusion criteria, quality and risk of bias assessment (Strengthening the Reporting of Observational Studies in Epidemiology and Newcastle-Ottawa criteria), leaving 22 studies. The meta-analysis followed Meta-analysis Of Observational Studies in Epidemiology criteria and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled ORs, weights and 95% CIs were calculated using a random-effects model., Results: This meta-analysis included 232 519 participants from 22 studies and showed an increased likelihood of no CP during an MI for those with DM, compared with those without. This was 43% higher in patients with DM in the cohort and cross-sectional studies (OR: 1.43; 95% CI: 1.26 to 1.62), and 44% higher in case-control studies (OR: 1.44; 95% CI: 1.11 to 1.87)., Conclusion: In patients with an MI, patients with DM are less likely than those without to have presentations with CP recorded. Clinicians should consider an MI diagnosis when patients with DM present with atypical symptoms and treatment protocols should reflect this, alongside an increased patient awareness on this issue., Prospero Registration Number: CRD42017058223., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

177 Lu-prostate-specific membrane antigen-617 ( 177 Lu-PSMA-617) is an effective therapy for metastatic castration-resistant prostate cancer (mCRPC), with evidence of improved survival over standard care. The VISION trial inclusion criteria required a metastatic lesion-to-liver ratio of greater than 1 on 68 Ga-PSMA-11 PET scans. We aimed to determine whether an equivalent ratio is suitable for a SPECT tracer, 99m Tc-MIP-1404, and to compare lesion and lesion-to-normal-organ ratios between the 2 radiotracers. Methods: Two cohorts of patients with mCRPC matched for age, prostate-specific antigen level, and total Gleason score, with either 99m Tc-MIP-1404 SPECT/CT ( n = 25) or 68 Ga-PSMA-11 PET/CT ( n = 25) scans, were included for analysis. Up to 3 lesions in each site (prostate/prostate bed, lymph nodes, bone and soft-tissue metastases) as well as normal liver, parotid gland, spleen, and mediastinal blood-pool SUV max were measured. Results: 99m Tc-MIP-1404 SPECT lesion SUV max was not significantly different from 68 Ga-PSMA-11 PET (median, 18.2 vs. 17.3; P = 0.93). However, 99m Tc-MIP-1404 liver SUV max was higher (median, 8.5 vs. 5.8; P = 0.002) and lesion-to-liver ratios were lower (median, 2.7 vs. 3.5; P = 0.009). There was no significant difference in parotid gland or splenic SUV max or lesion-to-parotid gland ratios between the 2 tracers although there was a small difference in lesion-to-spleen ratios ( P = 0.034). Conclusion: There are differences in biodistribution and, in particular, liver activity, between 68 Ga-PSMA-11 and 99m Tc-MIP-1404. Therefore, if 99m Tc-MIP-1404 is used to assess eligibility for 177 Lu-PSMA-617 therapy, a lower adjusted lesion-to-liver ratio should be used., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Objectives: The aim of this study was to characterize national variation in radionuclide calibrator activity response to a single National Institute of Standards and Technology (NIST) traceable reference Ge source used as a surrogate for F at clinical PET centres in England using National Physical Laboratory approved techniques., Methods: Readings from 20 instruments at 13 centres using local F and Ge factor settings were recorded with the source located in vial and syringe positions. Ten repeat measurements were conducted to investigate repeatability using % coefficient of variability (COV). Comparison ratios to investigate accuracy were made between calibrator responses and decay-corrected NISTref reference activity for syringe and vial position measurements., Results: The maximum %COV was 0.79%, while 90, 95 and 80% of calibrators conformed to 5% accuracy for F syringe, Ge syringe and Ge vial position readings, respectively. We revealed a trend towards reduced bias in measurements using Veenstra devices for F and using Capintec devices for Ge factor settings., Conclusions: This study demonstrated good repeatability in local device measurements. In total, 70% of English calibrators tested and 88% of all measurements performed achieved 5% accuracy. While statistically significant bias was exhibited between different vendor equipment dependent upon radioisotope selected, our study recommends regular traceability checks for optimum instrument performance conducted within National Metrology Institutes guidelines.

Purpose: To investigate the value of 18 FDG PET/CT volumetric parameters in the prediction of overall survival (OS) in patients with pancreatic cancer and also, assess their independence relative to well-established clinico-pathological variables., Methods: We conducted a retrospective analysis of patients with a confirmed diagnosis of pancreatic cancer who underwent 18 FDG PET/CT. The tumour maximum standardised uptake value (SUV max ) in addition to SUV mean , metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated. The prognostic value of 18 FDG PET/CT and clinico-pathological parameters for OS were assessed using univariate and multivariable analyses., Results: A sum of 89 patients were analysed in this study. Median survival for patients categorised as having high TLG (≥55) and low TLG (<55) was 18 vs 5 months (p < 0.001). Similarly, the respective high vs low SUV mean , MTV and SUVmax were 18 vs 6 months (p = 0.001), 16 vs 6 months (p = 0.002) and 18 vs 6 months (p = 0.001). Univariate analysis showed SUV max, SUV mean, MTV, TLG, tumour size, tumour differentiation and presence of distant metastasis as prognostic factors for OS. On multivariable analysis, TLG (HR 2.0, 95% CI 1.26-3.18, p = 0.004) and the presence of distant metastasis (HR 3.37, 95% CI 1.97-5.77, p < 0.001) emerged as independent prognostic factors. Subgroup analysis identified TLG as the only significant PET metric after adjusting for the presence of distant metastasis., Conclusions: 18 FDG PET/CT is a useful tool in the preoperative evaluation of patients with pancreatic cancer. Tumour TLG offer an independent prognostic value in both potentially operable and metastatic disease settings., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: Harmonisation is the process whereby standardised uptake values from different scanners can be made comparable. This PET/CT pilot study aimed to evaluate the effectiveness of harmonisation of a modern scanner with image reconstruction incorporating resolution recovery (RR) with another vendor older scanner operated in two-dimensional (2D) mode, and for both against a European standard (EARL). The vendor-proprietary software EQ•PET was used, which achieves harmonisation with a Gaussian smoothing. A substudy investigated effect of RR on harmonisation., Methods: Phantom studies on each scanner were performed to optimise the smoothing parameters required to achieve successful harmonisation. 80 patients were retrospectively selected; half were imaged on each scanner. As proof of principle, a cohort of 10 patients was selected from the modern scanner subjects to study the effects of RR on harmonisation., Results: Before harmonisation, the modern scanner without RR adhered to EARL specification. Using the phantom data, filters were derived for optimal harmonisation between scanners and with and without RR as applicable, to the EARL standard. The 80-patient cohort did not reveal any statistically significant differences. In the 10-patient cohort SUVmax for RR > no RR irrespective of harmonisation but differences lacked statistical significance (one-way ANOVA F(3.36) = 0.37, p = 0.78). Bland-Altman analysis showed that harmonisation reduced the SUVmax ratio between RR and no RR to 1.07 (95% CI 0.96-1.18) with no outliers., Conclusions: EQ•PET successfully enabled harmonisation between modern and older scanners and against the EARL standard. Harmonisation reduces SUVmax and dependence on the use of RR in the modern scanner., Advances in Knowledge: EQ•PET is feasible to harmonise different PET/CT scanners and reduces the effect of RR on SUVmax., (© 2020 The Authors. Published by the British Institute of Radiology.)

This phase II trial was designed to determine the safety and efficacy of a modified paediatric risk-stratified protocol in young adults (18-30 years) with classical Hodgkin Lymphoma. The primary end-point was neurotoxicity rate. The incidence of grade 3 neurotoxicity was 11% (80% CI, 5-19%); a true rate of neuropathy of >15% cannot be excluded. Neuropathy and associated deterioration in quality of life was largely reversible. The overall response rate was 100% with 40% complete remission (CR) rate. Twelve months disease-free survival (DFS) was 91%. We demonstrate that a risk-stratified paediatric combined modality treatment approach can be delivered to young adults without significant irreversible neuropathy., (© 2019 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Hypoxic-ischemic (HI) encephalopathy is a major cause of neonatal mortality and morbidity, with a global incidence of 3 per 1,000 live births. Intrauterine or perinatal complications, including maternal infection, constitute a major risk for the development of neonatal HI brain damage. During HI, inflammatory response and oxidative stress occur, causing subsequent cell death. The presence of an infection sensitizes the neonatal brain, making it more vulnerable to the HI damage. Currently, therapeutic hypothermia is the only clinically approved treatment available for HI encephalopathy, however it is only partially effective in HI alone and its application in infection-sensitized HI is debatable. Therefore, there is an unmet clinical need for the development of novel therapeutic interventions for the treatment of HI. Such an alternative is targeting the complement system. Properdin, which is involved in stabilization of the alternative pathway convertases, is the only known positive regulator of alternative complement activation. Absence of the classical pathway in the neonatal HI brain is neuroprotective. However, there is a paucity of data on the participation of the alternative pathway and in particular the role of properdin in HI brain damage. Objectives: Our study aimed to validate the effect of global properdin deletion in two mouse models: HI alone and LPS-sensitized HI, thus addressing two different clinical scenarios. Results: Our results indicate that global properdin deletion in a Rice-Vannucci model of neonatal HI and LPS-sensitized HI brain damage, in the short term, clearly reduced forebrain cell death and microglial activation, as well as tissue loss. In HI alone, deletion of properdin reduced TUNEL+ cell death and microglial post-HI response at 48 h post insult. Under the conditions of LPS-sensitized HI, properdin deletion diminished TUNEL+ cell death, tissue loss and microglial activation at 48 h post-HI. Conclusion: Overall, our data suggests a critical role for properdin, and possibly also a contribution in neonatal HI alone and in infection-sensitized HI brain damage. Thus, properdin can be considered a novel target for treatment of neonatal HI brain damage., (Copyright © 2019 Sisa, Agha-Shah, Sanghera, Carno, Stover and Hristova.)

Objectives: To determine if unexpected aorta uptake seen in some patients is influenced by popular modern reconstruction algorithms using semi-quantitative and qualitative analysis., Methods: Twenty-five consecutive patients without suspected vascular disease were selected for 18 F-FDG positron emission tomography/ computed tomography (PET/CT) scanning and images of the aorta were created using iterative reconstruction (IT), IT + time of flight (TOF), IT + TOF + point spread function correction (referred collectively as UHD) with and without metal artefact reduction (MAR) algorithms. An experienced radiologist created aorta and blood pool (BP) regions of interests then copied these to all reconstructions for accurate positioning before recording target aorta standardized-uptake-values (SUV max ) and background BP SUV mean . Furthermore, target-to-background ratio (TBR max ) was defined by aorta SUV max -to-BP SUV mean ratio for more analysis., Results: For aorta SUV max with IT, IT + TOF, UHD, UHD + MAR reconstructions the mean ± standard deviation recorded were 2.15±0.43, 2.25±0.51, 2.25±0.45 and 2.09±0.4, respectively. Values for BP SUV mean were 1.61±0.31, 1.58±0.28, 1.58±0.28 and 1.47±0.25, respectively. Likewise, for TBR max these were 1.35±0.19, 1.43±0.21, 1.43±0.19, 1.43±0.18, respectively. ANOVA analysis revealed no significant differences for aorta SUV max (F(0.86) p=0.46), BP SUV mean (F(1.22) p=0.31) or TBR max (F(0.99) p=0.4). However, the qualitative visual analysis revealed significant differences between IT + TOF with UHD (p=0.02) or UHD + MAR (p=0.02)., Conclusion: Reconstruction algorithm effect on aorta SUV max or BP SUV mean or TBR max was not statistically significant. However, qualitative visual analysis showed significant differences between IT + TOF as compared with UHD or UHD + MAR reconstructions. Harmonization of techniques with a larger patient cohort is recommended in future clinical trials.

Background: Pancreatic cancer diagnosis and staging can be difficult in 10-20% of patients. Positron emission tomography (PET)/computed tomography (CT) adds precise anatomical localisation to functional data. The use of PET/CT may add further value to the diagnosis and staging of pancreatic cancer., Objective: To determine the incremental diagnostic accuracy and impact of PET/CT in addition to standard diagnostic work-up in patients with suspected pancreatic cancer., Design: A multicentre prospective diagnostic accuracy and clinical value study of PET/CT in suspected pancreatic malignancy., Participants: Patients with suspected pancreatic malignancy., Interventions: All patients to undergo PET/CT following standard diagnostic work-up., Main Outcome Measures: The primary outcome was the incremental diagnostic value of PET/CT in addition to standard diagnostic work-up with multidetector computed tomography (MDCT). Secondary outcomes were (1) changes in patients' diagnosis, staging and management as a result of PET/CT; (2) changes in the costs and effectiveness of patient management as a result of PET/CT; (3) the incremental diagnostic value of PET/CT in chronic pancreatitis; (4) the identification of groups of patients who would benefit most from PET/CT; and (5) the incremental diagnostic value of PET/CT in other pancreatic tumours., Results: Between 2011 and 2013, 589 patients with suspected pancreatic cancer underwent MDCT and PET/CT, with 550 patients having complete data and in-range PET/CT. Sensitivity and specificity for the diagnosis of pancreatic cancer were 88.5% and 70.6%, respectively, for MDCT and 92.7% and 75.8%, respectively, for PET/CT. The maximum standardised uptake value (SUV max. ) for a pancreatic cancer diagnosis was 7.5. PET/CT demonstrated a significant improvement in relative sensitivity ( p  = 0.01) and specificity ( p  = 0.023) compared with MDCT. Incremental likelihood ratios demonstrated that PET/CT significantly improved diagnostic accuracy in all scenarios ( p  < 0.0002). PET/CT correctly changed the staging of pancreatic cancer in 56 patients ( p  = 0.001). PET/CT influenced management in 250 (45%) patients. PET/CT stopped resection in 58 (20%) patients who were due to have surgery. The benefit of PET/CT was limited in patients with chronic pancreatitis or other pancreatic tumours. PET/CT was associated with a gain in quality-adjusted life-years of 0.0157 (95% confidence interval -0.0101 to 0.0430). In the base-case model PET/CT was seen to dominate MDCT alone and is thus highly likely to be cost-effective for the UK NHS. PET/CT was seen to be most cost-effective for the subgroup of patients with suspected pancreatic cancer who were thought to be resectable., Conclusion: PET/CT provided a significant incremental diagnostic benefit in the diagnosis of pancreatic cancer and significantly influenced the staging and management of patients. PET/CT had limited utility in chronic pancreatitis and other pancreatic tumours. PET/CT is likely to be cost-effective at current reimbursement rates for PET/CT to the UK NHS. This was not a randomised controlled trial and therefore we do not have any information from patients who would have undergone MDCT only for comparison. In addition, there were issues in estimating costs for PET/CT. Future work should evaluate the role of PET/CT in intraductal papillary mucinous neoplasm and prognosis and response to therapy in patients with pancreatic cancer., Study Registration: Current Controlled Trials ISRCTN73852054 and UKCRN 8166., Funding: The National Institute for Health Research Health Technology Assessment programme.

Background: Planned neck dissection (ND) after radical chemoradiotherapy (CRT) for locally advanced nodal metastases in patients with head and neck squamous cell carcinoma (HNSCC) remains controversial. Thirty per cent of ND specimens show histological evidence of tumour. Consequently, a significant proportion of clinicians still practise planned ND. Fludeoxyglucose positron emission tomography (PET)-computerised tomography (CT) scanning demonstrated high negative predictive values for persistent nodal disease, providing a possible alternative paradigm to ND. Evidence is sparse and drawn mainly from retrospective single-institution studies, illustrating the need for a prospective randomised controlled trial., Objectives: To determine the efficacy and cost-effectiveness of PET-CT-guided surveillance, compared with planned ND, in a multicentre, prospective, randomised setting., Design: A pragmatic randomised non-inferiority trial comparing PET-CT-guided watch-and-wait policy with the current planned ND policy in HNSCC patients with locally advanced nodal metastases and treated with radical CRT. Patients were randomised in a 1 : 1 ratio. Primary outcomes were overall survival (OS) and cost-effectiveness [incremental cost per incremental quality-adjusted life-year (QALY)]. Cost-effectiveness was assessed over the trial period using individual patient data, and over a lifetime horizon using a decision-analytic model. Secondary outcomes were recurrence in the neck, complication rates and quality of life. The recruitment of 560 patients was planned to detect non-inferior OS in the intervention arm with a 90% power and a type I error of 5%, with non-inferiority defined as having a hazard ratio (HR) of no higher than 1.50. An intention-to-treat analysis was performed by Cox's proportional hazards model., Settings: Thirty-seven head and neck cancer-treating centres (43 NHS hospitals) throughout the UK., Participants: Patients with locally advanced nodal metastases of oropharynx, hypopharynx, larynx, oral or occult HNSCC receiving CRT and fit for ND were recruited., Intervention: Patients randomised to planned ND before or after CRT (control), or CRT followed by fludeoxyglucose PET-CT 10-12 weeks post CRT with ND only if PET-CT showed incomplete or equivocal response of nodal disease (intervention). Balanced by centre, planned ND timing, CRT schedule, disease site and the tumour, node, metastasis stage., Results: In total, 564 patients were recruited (ND arm, n  = 282; and surveillance arm, n  = 282; 17% N2a, 61% N2b, 18% N2c and 3% N3). Eighty-four per cent had oropharyngeal cancer. Seventy-five per cent of tested cases were p16 positive. The median time to follow-up was 36 months. The HR for OS was 0.92 [95% confidence interval (CI) 0.65 to 1.32], indicating non-inferiority. The upper limit of the non-inferiority HR margin of 1.50, which was informed by patient advisors to the project, lies at the 99.6 percentile of this estimate ( p  = 0.004). There were no differences in this result by p16 status. There were 54 NDs performed in the surveillance arm, with 22 surgical complications, and 221 NDs in the ND arm, with 85 complications. Quality-of-life scores were slightly better in the surveillance arm. Compared with planned ND, PET-CT surveillance produced an incremental net health benefit of 0.16 QALYs (95% CI 0.03 to 0.28 QALYs) over the trial period and 0.21 QALYs (95% CI -0.41 to 0.85 QALYs) over the modelled lifetime horizon., Limitations: Pragmatic randomised controlled trial with a 36-month median follow-up., Conclusions: PET-CT-guided active surveillance showed similar survival outcomes to ND but resulted in considerably fewer NDs, fewer complications and lower costs, supporting its use in routine practice., Future Work: PET-CT surveillance is cost-effective in the short term, and long-term cost-effectiveness could be addressed in future work., Trial Registration: Current Controlled Trials ISRCTN13735240., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 17. See the NIHR Journals Library website for further project information.

This article examines how individuals are reflexive beings who interpret the world in relation to things that matter to them, and how charitable acts are evaluated and embedded in their lives with different degrees of meaning and importance. Rather than framing the discussion of charitable practices in terms of an altruism/egoism binary or imputing motivations and values to social structures, the article explains how reflexivity is an important and neglected dimension of social practices, and how it interacts with sympathy, sentiments and discourses to shape giving. The study also shows that there are different modes of reflexivity, which have varied effects on charity and volunteering.

This paper examines how charitable giving offers an example of lay morality, reflecting people's capacity for fellow-feeling, moral sentiments, personal reflexivity, ethical dispositions, moral norms and moral discourses. Lay morality refers to how people should treat others and be treated by them, matters that are important for their subjective and objective well-being. It is a first person evaluative relation to the world (about things that matter to people). While the paper is sympathetic to the 'moral boundaries' approach, which seeks to address the neglect of moral evaluations in sociology, it reveals this approach to have some shortcomings. The paper argues that although morality is always mediated by cultural discourses and shaped by structural factors, it also has a universalizing character because people have fellow-feelings, shared human conditions, and have reason to value.