Alpha-fetoprotein detection of hepatocellular carcinoma leads to a standardized analysis of dynamic AFP to improve screening based detection

Detection of hepatocellular carcinoma (HCC) through screening can improve outcomes. However, HCC surveillance remains costly, cumbersome and suboptimal. We tested whether and how serum Alpha-Fetoprotein (AFP) should be used in HCC surveillance. Record linkage, dedicated pathways for management and AFP data-storage identified i) consecutive highly characterised cases of HCC diagnosed in 2009-14 and ii) a cohort of ongoing HCC-free patients undergoing regular HCC surveillance from 2009. These two well-defined Scottish patient cohorts enabled us to test the utility of AFP surveillance. Of 04 cases of HCC diagnosed over 6 years, 42% (129) were identified by a dedicated HCC surveillance programme. Of these 129, 47% (61) had a detectable lesion first identified by screening ultrasound (US) but 38% (49) were prompted by elevated AFP. Despite pre-HCC diagnosis AFP >20kU/L being associated with poor outcome, 'AFP-detected' tumours were offered potentially curative management as frequently as 'US-detected' HCCs; and had comparable survival. Linearity of serial log10 -transformed AFPs in HCC cases and in the screening 'HCC-free' cohort (n = 1509) provided indicators of high-risk AFP behaviour in HCC cases. An algorithm was devised in static mode, then tested dynamically. A case/control series in hepatitis C related disease demonstrated highly significant detection (p-5) of patients at high risk of developing HCC. These data support the use of AFP in HCC surveillance. We show proof-of-principle that an automated and further refineable algorithmic interpretation of AFP can identify patients at higher risk of HCC. This approach could provide a cost-effective, user-friendly and much needed addition to US surveillance

Osteoarthritis: 119. The Effectiveness of Exercise Therapy with and without Manual Therapy for Hip Osteoarthritis: A Multicentre Randomised Controlled Trial

Background: Current evidence indicates that exercise therapy (ET) has a short and medium-term benefit for hip osteoarthritis (OA), but evidence is inconclusive regarding the effect of manual therapy (MT). The primary aim of this randomised controlled trial was to determine the effectiveness of ET with and without MT on clinical outcomes for individuals with hip OA. A secondary aim was to ascertain the effect of an 8-week waiting period on outcomes. Methods: 131 men and women with hip OA recruited in four hospitals were initially randomised to one of three groups: ET (n = 45), a combination of ET and MT (n = 43) and wait-list control (n = 43). The two intervention groups underwent individualised ET or ET/MT for 8 weeks. Patients in the control group waited 8 weeks and were randomised to receive either ET or ET/MT after 9 week follow-up, and pooled with original treatment group data: ET (n = 66) and ET/ MT (n = 65). All participants were followed up at 9 and 18 weeks and the control group was reassessed at 27 weeks (18 weeks post-treatment) by the same blinded assessor. The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Other outcomes included sit-to-stand, 50-foot walk test, pain severity, hip range of motion (ROM), anxiety, depression, quality of life (QOL), analgesic usage, physical activity, patient-perceived change and patient satisfaction. Intention-to-treat analysis was performed to determine within-group change and between-group differences for the three groups at baseline and 9 weeks, and the two treatment groups at baseline, 9 and 18 weeks. Results: Eight patients (6.1%) were lost to follow-up at 9 weeks and 19 (14.5%) were lost to follow-up by 18 weeks. Both ET (n = 66) and ET/MT groups (n = 65) showed significant within-group improvements in WOMAC, pain severity, sit-to-stand and HROM measures at 9 weeks, which were still evident at 18 weeks. There was no significant within-group change in anxiety, depression, QOL, analgesic usage, 50-foot walk test or physical activity. There was no significant difference between the two intervention groups for any of the outcomes. Regarding the results of the original ET, ET/MT and control group allocation, there was a significant improvement in one or both ET and ET/MT groups compared with the control group in the same outcomes, as well as patient perceived improvement at 9 weeks. There was no significant difference between the three groups in analgesic usage, WOMAC stiffness subscale, sit-to-stand and 50 foot walk tests, QOL and physical activity. There was an overall deterioration in anxiety and depression scores. Conclusions: The addition of MT to an 8 week programme of ET for hip OA resulted in similar improvements in pain, function and ROM at 9 and 18 weeks. The significant improvement which occurred in the same outcomes in the two treatment groups compared with a wait-list control of 8 weeks has implications for waiting list management Disclosure statement: The authors have declared no conflicts of interes

Cognitive mechanisms associated with auditory sensory gating

Sensory gating is a neurophysiological measure of inhibition that is characterised by a reduction in the P50 event-related potential to a repeated identical stimulus. The objective of this work was to determine the cognitive mechanisms that relate to the neurological phenomenon of auditory sensory gating. Sixty participants underwent a battery of 10 cognitive tasks, including qualitatively different measures of attentional inhibition, working memory, and fluid intelligence. Participants additionally completed a paired-stimulus paradigm as a measure of auditory sensory gating. A correlational analysis revealed that several tasks correlated significantly with sensory gating. However once fluid intelligence and working memory were accounted for, only a measure of latent inhibition and accuracy scores on the continuous performance task showed significant sensitivity to sensory gating. We conclude that sensory gating reflects the identification of goal-irrelevant information at the encoding (input) stage and the subsequent ability to selectively attend to goal-relevant information based on that previous identification

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM