D + T has shown long-term efficacy and a well-characterised safety profile in pts with BRAF-mutant melanoma in clinical trials; however, real-world evidence (RWE) is limited. ePROs compiled with digital solutions can allow for collection of symptom data, prompt reaction to medical events, and improved quality of life (QOL). Novartis and Kaiku Health codeveloped a platform for pts with high-risk stage III or unresectable/metastatic BRAF V600E/K–mutant melanoma to describe PROs during treatment with D + T and provide pt educational materials. 40 to 100 pts will be enrolled during treatment with D + T and followed for ≥ 6 mo to collect longitudinal PRO and clinical data. The primary endpoint is incidence of key symptoms such as fever, chills, fatigue, and nausea. Secondary endpoints include frequency, severity, and duration of symptoms; platform feasibility and impact on treatment interruptions and/or reductions and time on treatment; and machine learning (ML) modelling aimed at predicting symptom onset and continuity. At data cutoff for the interim analysis (22 Mar 2022), 49 pts were enrolled from 5 sites. The adoption rate was 92%, with 45/49 invited pts registered, with 66% using the module for ≥ 12 wk. The majority (65%) used mobile versions, and 76% read electronic educational materials. 39/45 pts reported a total of 7217 symptoms using the module with a 71% average weekly compliance, and 39 pts completed ≥ 1 QOL questionnaire. Median time spent on questionnaires ranged from ≈ 2-3 minutes. Common symptoms were fatigue (82%), headache (56%), cough (51%), and muscle pain (51%). 10 pts reported 19 cases of acute fever and were monitored using a fever management algorithm until resolution. ML models predicted symptom onset and continuity for 9 symptoms with good to excellent performance. Interim data suggest that modules are supporting pts while generating RWE, which opens the possibility of understanding safety profiles and QOL in this setting. Continued data collection and investigation of ML aim to better predict symptoms for earlier intervention.

Introduction Vascular adhesion protein (VAP)-1 is an adhesion molecule and potent amine-oxidase. Activation on hepatic sinusoidal endothelial cells (HSEC) leads to H2O2 release, NFκB activation and expression of gut-homing receptor MAdCAM-1, which promotes homing of gut-tropic lymphocytes to the liver. Given the proposed role of this pathway in hepatic disorders complicating inflammatory bowel disease (IBD); we quantified serum (sVAP-1) titre and intrahepatic/colonic enzyme activity in primary sclerosing cholangitis (PSC)/IBD, as well as investigated consequences of activation with variant amine substrates. Method sVAP-1 was quantified by ELISA in PSC (n = 105); PBC (90); AIH (99); IBD-alone (50) and healthy controls (21). Correlation with clinical outcome was assessed using Cox proportional hazards assumption/KM-estimates. VAP-1 activity was determined (Amplex red assay) in protein lysates extracted from (a) explanted liver (PSC=9; PBC=10, AIH=5, normal donor, n = 10) and (b) colonic resections (n = 7). Putative VAP-1 substrates were selected based on inclusion in the human metabolome database, and induced kinetic rates measured (Michaelis-Menton analysis). Induction of MAdCAM-1 on HSEC was evaluated quantitatively (cell-ELISA) and functionally (flow-adhesion assays). Results PSC patients had higher sVAP-1 concentration (median 517 ng/mL) than those with AIH (475), PBC (472), IBD-alone (413) and healthy controls (425) (p < 0.001). sVAP-1 tires >530 ng/ml in PSC were associated with significantly worse transplant-free survival (unadj. HR:2.94, p = 0.008), and retained independent predictive value when controlling for other significant risk factors (cirrhosis, ascending cholangitis and liver biochemistry; adj. HR:3.85, p = 0.003). Intrahepatic VAP-1 enzyme activity was significantly greater in PSC (227 pmol H2O2/min/mg protein) compared with PBC (124), AIH (128) and donor liver (109) (p < 0.001), yet comparable to activity in colonic tissue (220; p=n.s.). The substrate associated with highest VAP-1 enzymatic efficiency was cysteamine (kcat/Km:5.4 × 107); an amine secreted by Escherichia. which induces colitis in mice. Cysteamine+TNFa provision resulted in greater MAdCAM-1 expression by HSEC ELISA than that with other substrates or TNFa alone (p < 0.01), with increased a4b7-dependent adhesion under flow (p < 0.01). Conclusion Elevated levels of circulating sVAP-1 exist in PSC and predictive of poor outcome. Intrahepatic VAP-1 enzyme activity is also increased in PSC and akin to that seen in the colon. The ability of VAP-1 to catabolise amine substrates secreted by gut commensals/enteric pathogens, provides a theoretical link between altered colonic microbiota and mucosal immunity in the pathogenesis of PSC. Disclosure of interest None Declared.

Adaptive multirate (AMR) codec was standardised for GSM in 1999. AMR offers substantial improvement over previous GSM speech codecs in error robustness by adapting speech and channel coding depending on channel conditions. However, current standard do not exploit the multirate capability of AMR codec in source signal based adaptation that would optimise the average bit-rate vs. quality trade-off. This paper presents a source signal based rate adaptation algorithm for AMR codec in GSM system. Together with fast power control, it can be used to increase the system capacity and further increase the robustness of GSM AMR codec.

This paper studies the performance of adaptive multirate (AMR) voice service in GSM and WCDMA radio networks. The AMR voice codec and its utilization in GSM and WCDMA radio networks are first introduced. The effect of AMR to GSM and WCDMA spectral efficiency is evaluated. It is shown that AMR can improve GSM spectral efficiency 100-150% compared to the enhanced full rate (EFR) codec. AMR further allows the utilization of half-rate codec improving the hardware efficiency in GSM. In WCDMA networks, the AMR allows to make a trade-off between voice capacity and AMR bit rate. The paper also presents the future evolution of AMR voice coding for further enhancements of spectral efficiency and voice quality. The source based rate adaptation is shown to improve the AMR spectral efficiency up to 25%. The wideband AMR will bring improved audio quality for the wireless and fixed network.

This paper describes the adaptive multirate wideband (AMR-WB) speech codec selected by the Third Generation Partnership Project (3GPP) for GSM and the third generation mobile communication WCDMA system for providing wideband speech services. The AMR-WB speech codec algorithm was selected in December 2000 and the corresponding specifications were approved in March 2001. The AMR-WB codec was also selected by the International Telecommunication Union-Telecommunication Sector (ITU-T) in July 2001 in the standardization activity for wideband speech coding around 16 kb/s and was approved in January 2002 as Recommendation G.722.2. The adoption of AMR-WB by ITU-T is of significant importance since for the first time the same codec is adopted for wireless as well as wireline services. AMR-WB uses an extended audio bandwidth from 50 Hz to 7 kHz and gives superior speech quality and voice naturalness compared to existing second- and third-generation mobile communication systems. The wideband speech service provided by the AMR-WB codec will give mobile communication speech quality that also substantially exceeds (narrowband) wireline quality. The paper details AMR-WB standardization history, algorithmic description including novel techniques for efficient ACELP wideband speech coding and subjective quality performance of the codec.

This paper presents a source based rate adaptation concept for AMR wideband speech codec. The source based rate adaptation algorithm selects the multi rate codec mode based on the input speech characteristics and coding parameters to minimise the average bit rate. The presented concept introduces up to 50% reduction in average bit rate without any degradation in speech quality. The benefit of source based adaptation is in increasing the system capacity in conversational services as well as storage size in messaging type of applications.

This paper gives the history and performance of the Adaptive Multi-Rate Wideband (AMR-WB) speech codec recently selected by the Third Generation Partnership Project (3GPP) for GSM and the third generation mobile communication WCDMA system for providing wideband speech services. The AMR-WB speech codec algorithm was selected in December 2000, and the corresponding specifications were approved in March 2001. In July 2001, the AMR-WB codec was also selected by ITU-T in the standardization activity for wideband speech coding around 16 kbit/s. The adoption of AMR-WB by ITU-T is of significant importance since for the first time the same codec is adopted for wireless as well as wireline services. AMR-WB uses an extended audio bandwidth from 3.4 kHz to 7 kHz and gives superior speech quality and voice naturalness compared to 2(nd) and 3(rd) generation mobile communication systems.

This paper presents a novel method to estimate the pitch-lag in a speech codec. The pitch-lag is related to the fundamental frequency of the speech signal and an accurate estimation of this parameter is important for the subjective quality of the synthesised speech. A common problem in speech codecs is that the estimation of the pitch-lag often produces a multiple or a sub-multiple of the true pitch value. When these incorrect pitch-lag values are used in speech synthesis the subjective quality of the speech is degraded. This paper presents an improved method where the estimation of the pitch-lag parameter is biased towards the pitch-lag values of the previous speech segments resulting in a consistent set of consecutive pitch-lag values and a high quality reconstructed signal. The classification of speech into voiced and unvoiced parts is used when tracking the pitch-lag values and adapting the pitch track centered weighting function.

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