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Introduction: We describe a case of olanzapine-induced hypothermia and hand oedema in an older adult with behavioural and psychological symptoms of dementia (BPSD)., Case Presentation: An 82-year-old woman with hypothyroidism and dementia was reviewed by the geriatric team at a nursing home in view of lethargy and an unrecordable oral temperature. She was noted to have a bilateral hand oedema and right basal crackles. Investigations revealed high white cell count and inflammatory markers. She was treated as per hypothermia and communityacquired pneumonia protocols. The patient did not have the expected response to treatment. Olanzapine was tailed down and stopped with good effect as it was suspected to be a contributory cause to both the hypothermia and oedema., Discussion and Conclusion: Potentially inappropriate polypharmacy can be specifically targeted with effective deprescribing. Treatment review should be encouraged on a regular basis, especially in frail older adults with polypharmacy., (© Royal College of Physicians 2022. All rights reserved.)

We aim to study kinetics of anti-SARS-CoV-2 IgG antibody levels in subjects with COVID-19 for up to 11 months and the potential influential factors. The study was a prospective longitudinal study. The analyses were based on 77 serum/plasma samples with a mean of 4 samples per participant (range 1 - 18) in 20 participants with at least one positive Polymerase Chain Reaction testing result from 19 March 2020 up to 10 February 2021. Among the subjects (median age 34.5 years, 65% male), IgG level declined with the follow-up time (per month; geometric mean ratio [GMR] 0.73; 95% CI, 0.72 - 0.74). In a small sample of subjects from the general population with COVID-19, IgG levels declined non-linearly from month 2 to 11 with individual heterogeneity in quantity and changing speed and may be associated with gender, race and the loss of smell and taste., Competing Interests: Declaration of competing interests The authors declare that they have no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In clinical trials, traditionally only a limited number of 12-lead resting electrocardiograms (ECGs) can be recorded and, thus, long intervals may elapse between assessment timepoints and valuable information may be missed during times when patients' cardiac electrical activity is not being monitored. These limitations have led to the increasing use of Holter recorders which provide continuous data registrations while reducing the burden on patients and freeing up time for clinical trial staff to perform other tasks. However, there is a shortage of data comparing the two approaches. In this study, data from a randomized, double-blind, four-period, crossover thorough QT study in 40 healthy subjects were used to compare continuous 12-lead Holter recordings to standard 12-lead resting ECGs which were recorded in parallel. Heart rate and QT interval data were estimated by averaging three consecutive heartbeats. Values exceeding the sample average by more than 5% were tagged as outliers and excluded from the analysis. Visual comparisons of the ECG waveforms of the Holter signal showed a good correlation with resting ECGs at matching timepoints. Resting ECG data revealed sex differences that Holter data did not show. Specifically, women were found to have a longer QTcF of 20 ms, while men had a lower heart rate. We found that continuous recordings provided a more accurate reflection of changes in cardiac electrical activity over 24 hr. However, manual adjudication is still required to ensure the quality and accuracy of ECG data, and that only artifacts are removed thereby avoiding loss of true signals., (© 2021 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Nolasiban is an orally active oxytocin receptor antagonist being developed to increase the efficiency of assisted reproductive technologies. This study evaluated the pharmacokinetics, pharmacodynamics, and cardiac safety of nolasiban in 45 healthy women of child-bearing age. Nolasiban was administered in a fasted state with a standardised lunch served 4.5 h post-dose. Concentration-effect modelling was used to assess the effect of two dosages of nolasiban (900 mg and 1800 mg) on QTc following single-dose administration. We found no significant change in QTc at all tested dosages. Two-sided 90% confidence intervals of geometric mean C max for estimated QTc effects of nolasiban were below the threshold of regulatory concern. The sensitivity of the assay to detect small changes in QTc was confirmed by a significant shortening of QTc between 2 and 4 h after consumption of a meal, which served to validate the model. Independent of the nolasiban assessment, this study also explored the effects of sex hormones on ECG parameters, especially QT subintervals. We found a significant relationship between JTpc and oestradiol. Heart rate was negatively correlated with progesterone. This study confirms the cardiovascular safety of nolasiban and describes relationships of sex hormones and ECG parameters.

Background: Women living with HIV (WLWH) are at higher risk of acquisition and progression of human papillomavirus (HPV) infection. Evidence on effect of HPV vaccination in this population is limited., Methods: This phase IV randomized controlled observer-blind study assessed immunogenicity and safety of two HPV vaccines (AS04-HPV-16/18 vs. 4vHPV) given in WLWH (stage 1) and HIV- females aged 15-25 years. Co-primary endpoints were to demonstrate, in WLWH subjects, non-inferiority (and if demonstrated, superiority) of AS04-HPV-16/18 vs. 4vHPV for HPV-16 and HPV-18 by pseudovirion-based neutralization assay (PBNA) at month 7 and safety. Non-inferiority criteria was lower limit (LL) of the 95% confidence interval (CI) of the GMT ratio AS04-HPV-16/18/4vHPV above 0.5, in the according to protocol population. NCT01031069., Findings: Among 873 subjects recruited between 26-Oct-2010 and 14-May-2015, 546 were randomized (1:1) and received at least one vaccine dose (total vaccinated cohort, TVC): 257 were WLWH (129 AS04-HPV-16/18; 128 4vHPV) and 289 were subjects without HIV (144 AS04-HPV-16/18; 145 4vHPV). Baseline CD4 cell count in WLWH was at least 350 cells/mm 3 .At month 7, AS04-HPV-16/18 showed immunological superiority to 4vHPV in WLWH. Neutralizing anti-HPV-16 and HPV-18 antibody GMTs were 2·74 (95% CI: 1·83; 4·11) and 7·44 (95% CI: 4·79; 11·54) fold higher in AS04-HPV-16/18 vs. 4vHPV (LL of the GMT ratio >1 in TVC, p <0·0001), respectively. Similar results were observed by ELISA up to month 24.Solicited local and general symptoms were in line with product labels. The number of reported serious adverse events (SAEs) was balanced throughout the study., Interpretation: Both vaccines showed an acceptable safety profile in all subjects. Despite the absence of an immunological correlate of protection for HPV, differences in immune responses elicited by the vaccines especially for HPV-18 may translate into longer lasting or more robust protection against cervical cancer with the AS04-HPV-16/18 vaccine in WLWH., Competing Interests: N Folschweiller is an employee of the GSK group of companies and holds shares in the GSK group of companies. J Teixeira, S Joshi, K Supparatpinyo, and K Ruxrungtham report grants from the GSK group of companies for the conduct of the study. K Ruxrungtham also received honoraria or consultation fees from Merck, Roche, Jensen-Cilag, Tibotec, Myland and GPO (Governmental pharmaceutical organization, Thailand) and participated in a company sponsored speaker's bureau from Abbott, Gilead, Bristol-Myers Squibb, Merck, Roche, Jensen-Cilag, GSK, and Thai GPO. L Goldani, P Basu, C Roteli-Martins, B Grinsztejn, S Quintana, N Kumarasamy, S Poongulali and V Kulkarni report no conflict of interest. T Chotpitayasunondh reports grant for the study conduct and speaker honorarium outside of the present work, from the GSK group of companies. P Chetchotisakd reports grant from the GSK group of companies for the study conduct and from Gilead outside of the present work. L Lin, S Datta, D Descamps, F Tavares da Silva, D Friel, S Poncelet, and B Salaun are employees of the GSK group of companies and hold shares in the GSK group of companies. M Dodet, N Karkada are employees of the GSK group of companies. G Dubin was an employee of the GSK group of companies during the study conduct, holds shares in the GSK group of companies, and is currently an employee of Takeda Pharmaceuticals. F Struyf was an employee of the GSK group of companies during the study conduct, holds shares in the GSK group of companies, and is currently an employee of Janssen, Pharmaceutical Companies of Johnson & Johnson. M Hezareh reports consulting fees for her institution from the GSK group of companies. D Meric Camilleri was an employee of the GSK group of companies and held shares in the company at the time of the study. F Thomas-Jooris was an employee of the GSK group of companies at the time of the study and hold shares in the GSK group of companies., (© 2020 The Author(s).)

From neuroscience, brain imaging and the psychology of memory, we are beginning to assemble an integrated theory of the brain subsystems and pathways that allow the compression, storage and reconstruction of memories for past events and their use in contextualizing the present and reasoning about the future-mental time travel (MTT). Using computational models, embedded in humanoid robots, we are seeking to test the sufficiency of this theoretical account and to evaluate the usefulness of brain-inspired memory systems for social robots. In this contribution, we describe the use of machine learning techniques-Gaussian process latent variable models-to build a multimodal memory system for the iCub humanoid robot and summarize results of the deployment of this system for human-robot interaction. We also outline the further steps required to create a more complete robotic implementation of human-like autobiographical memory and MTT. We propose that generative memory models, such as those that form the core of our robot memory system, can provide a solution to the symbol grounding problem in embodied artificial intelligence. This article is part of the theme issue 'From social brains to social robots: applying neurocognitive insights to human-robot interaction'.

Generating complex, human-like behavior in a humanoid robot like the iCub requires the integration of a wide range of open source components and a scalable cognitive architecture. Hence, we present the iCub-HRI library which provides convenience wrappers for components related to perception (object recognition, agent tracking, speech recognition, and touch detection), object manipulation (basic and complex motor actions), and social interaction (speech synthesis and joint attention) exposed as a C++ library with bindings for Java (allowing to use iCub-HRI within Matlab) and Python. In addition to previously integrated components, the library allows for simple extension to new components and rapid prototyping by adapting to changes in interfaces between components. We also provide a set of modules which make use of the library, such as a high-level knowledge acquisition module and an action recognition module. The proposed architecture has been successfully employed for a complex human-robot interaction scenario involving the acquisition of language capabilities, execution of goal-oriented behavior and expression of a verbal narrative of the robot's experience in the world. Accompanying this paper is a tutorial which allows a subset of this interaction to be reproduced. The architecture is aimed at researchers familiarizing themselves with the iCub ecosystem, as well as expert users, and we expect the library to be widely used in the iCub community., (Copyright © 2018 Fischer, Puigbò, Camilleri, Nguyen, Moulin-Frier, Lallée, Metta, Prescott, Demiris and Verschure.)