King's College London

Recent studies have demonstrated the promise of psilocybin therapies in creating positive changes for those with poor mental health across multiple diagnostic categories, including major depressive disorder (MDD), end-of-life anxiety, and obsessive-compulsive disorder (OCD). While there may be a large population that is eligible to participate in psilocybin therapy based on psychiatric diagnosis and medical clearance, little attention has been given to intrapersonal and interpersonal factors that might influence patient's readiness (i.e., eligibility and capacity) for psychedelic interventions. This paper proposes that readiness assessment includes both intrapersonal and interpersonal factors in order to improve safety, patient care, and treatment outcomes. While at the present time a reliable and valid instrument has not been developed, we propose that three specific areas of focus - patient presentation, therapeutic alliance, and patient safety - may be used to establish a patient's readiness for psilocybin therapy, thus increasing therapy optimization and personalization.

Optical systems and genetic engineering technologies have made it possible to control neurons and unravel neuronal circuit behavior with high temporal and spatial resolution. The application of optogenetic strategies to understand the physiology of kisspeptin neuronal circuits has evolved in recent years among the neuroendocrine community. Kisspeptin neurons are fundamentally involved in controlling mammalian reproduction but also are implicated in numerous other physiological processes, including but not limited to feeding, energy expenditure, core body temperature and behavior. We conducted a review aiming to shed light on the novel findings obtained from in vitro and in vivo optogenetic studies interrogating kisspeptin neuronal circuits to date. Understanding the function of kisspeptin networks in the brain can greatly inform a wide range of clinical studies investigating infertility treatments, gender identity, metabolic disorders, hot flushes and psychosexual disorders.

Goal Management Training (GMT) improved self-reported executive functioning in a recent randomized, controlled trial in early intervention for psychosis participants. Little is known about the mechanism for this benefit, so this study investigates objectively measured executive function, the difference between subjective and objective executive function, independent living and employment status as potential moderators of efficacy of GMT. Baseline scores from 81 participants (GMT n = 39 vs Treatment-as-usual; TAU n = 42) were analyzed in a linear mixed model analysis for repeated measures as predictors of improvement on the self-reported Behavior Rating Inventory of Executive Function–Adult version (BRIEF-A) immediately and 30 weeks after GMT. Potential moderators were scores from objective measures of executive functioning, discrepancy between subjective and objective measures, independent living and employment status. Discrepancy was assessed by comparing four clusters of participants with differing patterns of scores. The effect of GMT remained significant regardless of initial objective executive functioning at baseline. Those with higher subjective complaints at baseline in two clusters with (i) both objective and subjective executive dysfunction, and (ii) mostly subjective executive dysfunction experienced greater change after treatment. Living arrangements or participation in education or work did not significantly moderate the effects of GMT. Poor performance on neuropsychological tasks is not an obstacle to making use of GMT, but further knowledge is needed about the benefits of strategy training for individuals with a combination of poor performance with few subjective complaints.

This paper examines the variations and derivations of the dual Euler-Rodrigues formula from various mathematical forms, including the matrix in 6 × 6, the dual matrix, Lie group SE(3) of the exponential map of the Lie algebra se(3), and the dual quaternion conjugation, and investigates their intrinsic connections. Based on the dual Euler-Rodrigues formula, the axis, the dual rotation angle, and the new traces are obtained by using the properties of the skew-symmetric matrices. In decomposing the Chasles’ motion, this paper examines two ways of realization of the motion based on the Mozzi-Chasles’ axis. With the equivalent motion, the paper relates the finite displacement screw matrix, the exponential map, and the dual quaternion conjugation to the dual Euler-Rodrigues formula and reveals their connection with the Mozzi-Chasles axis screw, whose parameters are used to construct the Lie algebra, the dual Euler-Rodrigues formula, and the dual quaternion. Further, using the Mozzi-Chasles axis screw, the paper presents a complete geometrical interpretation, including both the translation and rotation, and associates it with the algebraic presentation. By decomposing the equivalent translation induced by the rotation, the paper presents the mapping between the compound translation and the secondary part of the Mozzi-Chasles axis screw. With this map and the compound translation, the paper hence reveals the intrinsic connection between various presentations of rigid body transformations by formulating them into the dual Euler-Rodrigues formula and presents the relations of the exponential map of the Mozzi-Chasles axis screw to the finite displacement screw matrix and the dual Euler-Rodrigues formula, leading to the understanding of the various forms of a rigid body displacement in correspondence to the dual Euler-Rodrigues formula.

We investigate how changes in biotechnology are transforming the pursuit of human-specific models of disease and development. Our case study focuses on scientists who make human organoids. Organoids are stem cell-based three-dimensional multicellular living systems, made in labs, that mimic the function of human organs. Organoids create new opportunities for human health research, but we know little about how researchers understand the relationship between these model systems and the humans they are meant to represent. By analysing 25 interviews, complemented by observation and documentary research conducted in 2020–2022, we identify and discuss four themes that characterize how researcher's model humanness in organoids. For scientists, organoids are powerful tools to approximate the biology of human beings because they represent the closest thing to undertaking experiments on living humans, not previously possible. As laboratory tools, human organoids may replace the need for experimentation on animals, potentially contributing to the 3Rs of animal research (replacement, reduction, and refinement). Humanness is partly operationalized by modelling different human characteristics within organoids, such as male and female, different disease states, age, and other attributes. We find that human organoids are opening up previously closed spaces of experimentation and modelling in biomedicine. We argue that the humanness of organoid model systems are not a given but are enacted with and through a variety of scientific practices. These practices require critical attention from social scientists as the enactments of humanness being modelled in organoids have the potential to shape what and who counts as human in biomedical research.

Simulation is widely applied in robotics research to save time and resources. There have been several works to simulate optical tactile sensors that leverage either a smoothing method or Finite Element Method (FEM). However, elastomer deformation physics is not considered in the former method, whereas the latter requires a massive amount of computational resources like a computer cluster. In this work, we propose a pluggable and low computational cost simulator using the Taichi programming language for simulating optical tactile sensors, named as Tacchi . It reconstructs elastomer deformation using particles, which allows deformed elastomer surfaces to be rendered into tactile images and reveals contact information without suffering from high computational costs. Tacchi facilitates creating realistic tactile images in simulation, e.g., ones that capture wear-and-tear defects on object surfaces. In addition, the proposed Tacchi can be integrated with robotics simulators for a robot system simulation. Experiment results showed that Tacchi can produce images with better similarity to real images and achieved higher Sim2Real accuracy compared to the existing methods. Moreover, it can be connected with MuJoCo and Gazebo with only the requirement of 1G memory space in GPU compared to a computer cluster applied for FEM. With Tacchi, physical robot simulation with optical tactile sensors becomes possible. All the materials in this paper are available at https://github.com/zixichen007115/Tacchi .

Post-Traumatic Stress Disorder (PTSD) has been identified as an independent risk factor for cardiovascular disease, but the mechanisms of this relationship are not well understood. This study investigates the associations between PTSD symptom clusters (hyperarousal, intrusive thoughts, avoidance behaviours and emotional numbing) and mechanisms of cardiovascular disease including cardiometabolic effects, inflammation, and haemodynamic functioning. In the ADVANCE study cohort of UK male military personnel, 1111 participants were assessed for PTSD via questionnaire and cardiovascular risk via venous blood sampling, pulse wave analysis and dual energy x-ray absorptiometry between 2015 and 2020. Variable selection procedures were conducted to assess which of the symptom clusters if any were associated with cardiovascular risk outcomes. Associations were confirmed via robust regression modelling. Avoidance behaviours were associated with greater systolic Blood Pressure (BP) (Adjusted Coefficient (AC) 0.640 (95% Confidence Interval (CI) 0.065, 1.149). Emotional numbing was associated with greater estimated glucose disposal rate (AC -0.021 (95%CI -0.036, -0.005). Hyperarousal was associated with greater levels of (log)triglycerides (exponentiated-AC 1.009 (95%CI 1.002, 1.017). Intrusive thoughts were associated with greater visceral adipose tissue (AC 0.574 (95%CI 0.020, 1.250). Nonlinear relationships were observed between emotional numbing with heart rate and intrusive thoughts with systolic BP. Limited evidence is present for symptom associations with lipoproteins and pulse wave velocity. No associations were observed between PTSD symptom clusters and high sensitivity c-reactive protein, diastolic BP, total cholesterol, or haemoglobin fasting glucose. In conclusion, symptom clusters of PTSD were associated with increased cardiovascular risk via cardiometabolic and haemodynamic functioning mechanisms, but not inflammation.

Understanding how the work environment impacts health behaviours is essential to a life course approach in public health nutrition. A roundtable event ‘Workplace Diet and Health – priorities for researchers and practitioners’ was held by the Nutrition Society in October 2022. The overarching aims of the roundtable event were to consider (i) the relevance of nutritional wellbeing for employers and organisations, (ii) the research priorities for workplace diet and health and (iii) how researchers and practitioners can work with stakeholders in the development and testing of workplace diet and health interventions and nutritional education. Participants represented a range of stakeholders including dietetic and nutrition professionals working in workplace health, academics and science communication with an interest in workplace diet and health, non-governmental organisations and providers of workplace nutritional health and wellbeing programmes. All roundtable participants agreed that good nutrition and access to healthy food at work was part of corporate responsibility comparable to that of health and safety provision. It was recognised that nutritional wellbeing was not seen as a priority by many companies due to the complexity and wide range of employee health and wellbeing options available and the perceived lack of clear financial benefit. Three priority areas were identified and agreed upon by roundtable participants: (1) strengthening the evidence base to demonstrate the tangible benefit of nutritional wellbeing interventions in the workplace, (2) creating a knowledge exchange hub to share best practices and experiences of working across sectors and (3) expand stakeholder engagement in workplace nutritional wellbeing.

Kaposi sarcoma-associated herpesvirus (KSHV) causes Kaposi sarcoma (KS). The risk of KS is amplified in HIV-immunosuppressed individuals and antiretroviral therapy (ART) reduces KS incidence. Reliable data on the relationship between these factors are lacking in Africa. We used questionnaires and serum from 7,886 black South Africans (18-74 years) with incident cancer, recruited between 1995 and 2016. ART rollout started in 2004. We measured associations between KS, HIV-1 and KSHV before and after ART rollout. We measured seropositivity to HIV-1, KSHV latency-associated nuclear antigen (LANA) and glycoprotein (K8.1) and calculated case-control-adjusted odds ratios (ORadj ) and 95% Confidence Intervals (CI) in relation to KS and KSHV infection, before (1995-2004), early (2005-2009) and late (2010-2016) ART rollout periods. KSHV seropositivity among 1,237 KS cases was 98%. Among 6,649 controls, KSHV seropositivity was higher in males (ORadj =1.4 [95%CI1.23-1.52]), in persons with HIV, (ORadj =4.2 [95%CI3.74-4.73]) and lower in high school leavers (ORadj =0.7 [95%CI0.59-0.83]). KSHV seropositivity declined over the three ART rollout periods (37%, 28%, 28% Ptrend <0.001) coinciding with increases in high school leavers over the same periods (46%, 58% and 67%, Ptrend <0.001). HIV-1 seroprevalence increased from 10% in the pre-ART period to 22% in the late ART period (Ptrend <0.001). Compared to HIV-1 and KSHV seronegatives, KSHV seropositives yielded an OR for KS of 26 (95%CI11-62) in HIV-1 seronegative participants and an OR of 2501 (95%CI1083-5776) in HIV-1 seropositive participants. HIV-1 increases the risk of KS in those infected with KSHV by 100-fold. Declines in KSHV seroprevalence coincide with ART rollout and with improvements in educational standards and general hygiene.

Aims: Left atrial volume is commonly estimated using the bi-plane area-length method from two-chamber (2CH) and four-chamber (4CH) long axes views. However, this can be inaccurate due to a violation of geometric assumptions. We aimed to develop a deep learning neural network to infer 3D left atrial shape, volume and surface area from 2CH and 4CH views. Methods and results: A 3D UNet was trained and tested using 2CH and 4CH segmentations generated from 3D coronary computed tomography angiography (CCTA) segmentations (n = 1700, with 1400/100/200 cases for training/validating/testing). An independent test dataset from another institution was also evaluated, using cardiac magnetic resonance (CMR) 2CH and 4CH segmentations as input and 3D CCTA segmentations as the ground truth (n = 20). For the 200 test cases generated from CCTA, the network achieved a mean Dice score value of 93.7%, showing excellent 3D shape reconstruction from two views compared with the 3D segmentation Dice of 97.4%. The network also showed significantly lower mean absolute error values of 3.5 mL/4.9 cm2 for LA volume/surface area respectively compared to the area-length method errors of 13.0 mL/34.1 cm2 respectively (P < 0.05 for both). For the independent CMR test set, the network achieved accurate 3D shape estimation (mean Dice score value of 87.4%), and a mean absolute error values of 6.0 mL/5.7 cm2 for left atrial volume/surface area respectively, significantly less than the area-length method errors of 14.2 mL/19.3 cm2 respectively (P < 0.05 for both). Conclusions: Compared to the bi-plane area-length method, the network showed higher accuracy and robustness for both volume and surface area.

Research drives innovation however recently Clinical Radiology has been overwhelmed by increased clinical demand, workforce shortages and lack of funding/ protected research time. The newly released 2023 radiology speciality application process gives research a lower priority compared to other domains such as audit which is concerning given the current lack of research culture within the specialty. It is vital for the future radiology workforce to engage with research and in order to fulfil the Royal College of Radiologist's new curriculum aims of strengthening research within training, we must continue attracting the brightest and best candidates and ensure research remains a priority.

Objective To determine the effect of early childhood development interventions delivered by healthcare providers (HCP-ECD) on child cognition and maternal mental health. Design Systematic review, meta-analysis. Setting Healthcare setting or home. Participants Infants under 1 month of age. Interventions HCP-ECD interventions that supported responsive caregiving, early learning and motor stimulation. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, Database of Abstracts of Reviews of Effects and Cochrane Database of Systematic Reviews were searched until 15 November 2021. Studies reporting prespecified outcomes were pooled using standard meta-analytical methods. Main outcome measures Cognitive development in children at 0–36 months. Results Forty-two randomised controlled trials with 15 557 infants were included in the narrative synthesis. Twenty-seven trials were included in the meta-analyses. Pooled data from 13 trials suggest that HCP-ECD interventions may improve cognitive outcomes in children between 0 and 36 months (Bayley Scales of Infant Development version IIII (BSID-III) mean difference (MD) 2.65; 95% CI 0.61 to 4.70; 2482 participants; low certainty of evidence). Pooled data from nine trials suggest improvements in motor development (BSID-III MD 4.01; 95% CI 1.54 to 6.48; 1437 participants; low certainty of evidence). There was no evidence of improvement in maternal mental health (standardised MD −0.13; 95% CI −0.28 to 0.03; 2806 participants; 11 trials; low certainty of evidence). Conclusions We report promising evidence, particularly for cognitive and motor outcomes, of the effect of HCP-ECD interventions. However, effect sizes were small, and the certainty of evidence ranged from very low to moderate. Additional high-quality research is required.

In some clinical scenarios, for example, severe sepsis caused by extensively drug resistant bacteria, there is uncertainty between many common treatments, but a conventional multiarm randomized trial is not possible because individual participants may not be eligible to receive certain treatments. The Personalised Randomized Controlled Trial design allows each participant to be randomized between a "personalised randomization list" of treatments that are suitable for them. The primary aim is to produce treatment rankings that can guide choice of treatment, rather than focusing on the estimates of relative treatment effects. Here we use simulation to assess several novel analysis approaches for this innovative trial design. One of the approaches is like a network meta-analysis, where participants with the same personalised randomization list are like a trial, and both direct and indirect evidence are used. We evaluate this proposed analysis and compare it with analyses making less use of indirect evidence. We also propose new performance measures including the expected improvement in outcome if the trial's rankings are used to inform future treatment rather than random choice. We conclude that analysis of a personalized randomized controlled trial can be performed by pooling data from different types of participants and is robust to moderate subgroup-by-intervention interactions based on the parameters of our simulation. The proposed approach performs well with respect to estimation bias and coverage. It provides an overall treatment ranking list with reasonable precision, and is likely to improve outcome on average if used to determine intervention policies and guide individual clinical decisions.

Background: This study investigates the longitudinal role of interpretation biases in the development and maintenance of health anxiety during the pandemic. Individual differences in behavioural responses to the virus outbreak and decision-making were also examined. Methods: Two-hundred and seventy-nine individuals from a pre-pandemic study of interpretation bias and health anxiety completed an online survey during the third wave of the COVID-19 pandemic in Hong Kong. Participants’ health anxiety, interpretation biases, and COVID-specific behaviours (i.e., practice of social distancing, adherence to preventive measures, information seeking), and health decision-making were assessed. Results: Pre-pandemic tendencies to interpret ambiguous physical sensations as signals for illness did not predict health anxiety during the pandemic, b = -0.020, SE = 0.024, t = -0.843, p = .400, 99% CI [-0.082, 0.042], but were associated with a preference for risky treatment option for COVID-19, b = 0.026, SE = 0.010, Wald = 2.614, p = .009, OR = 1.026, 99% CI [1.001, 1.054]. Interpretation biases and health anxiety symptoms during the pandemic were associated with each other and were both found to be significant predictors of practice of social distancing, adherence to preventive measures, and information seeking behaviour. Conclusions: This study adds to the growing evidence of the role of interpretation biases in health anxiety and the way that people respond to the ongoing pandemic.

Objective This qualitative study examines the linguistic features associated with postpartum depression. Methods In this longitudinal online study, 53 mothers completed self-report questionnaires assessing symptoms of postpartum depression and an expressive writing exercise about their pregnancy and birth. Mothers were randomly divided into two groups (intervention and control groups). Linguistic Inquiry and Word Count [LIWC] was used to examine the written data for depression and no depression groups. Results The overall use of words varied depending on the severity of depressive symptoms. Negative emotions and introspective terms were associated with depression and lower use of first-person plural pronouns but not singular pronouns. Additionally, the groups of individuals with depression showed a positive correlation between depressive symptoms and words referring to friends, leisure activities, the body, breastfeeding, exercise, and eating attitudes. Conclusion In addition to self-disclosure, word analysis and appropriate categorization could be useful for perinatal symptomatology in pregnant women, and interestingly also a meaningful tool that can be taught and used as a preventive care measure among pregnant and postpartum women.

Problem Maternity care underwent substantial reconfiguration in the United Kingdom during the COVID-19 pandemic. Background COVID-19 posed an unprecedented public health crisis, risking population health and causing a significant health system shock. Aim To explore the psycho-social experiences of women who received maternity care and gave birth in South London during the first ‘lockdown’. Methods We recruited women (N=23) to semi-structured interviews, conducted virtually. Data were recorded, transcribed, and analysed by hand. A Classical Grounded Theory Analysis was followed including line-by-line coding, focused coding, development of super-categories followed by themes, and finally the generation of a theory. Findings Iterative and inductive analysis generated six emergent themes, sorted into three dyadic pairs: 1 & 2: Lack of relational care vs. Good practice persisting during the pandemic; 3 & 4: Denying the embodied experience of pregnancy and birth vs. Trying to keep everyone safe; and 5 & 6: Removed from support network vs. Importance of being at home as a family. Together, these themes interact to form the theory: ‘Navigating uncertainty alone’. Discussion Women’s pregnancy and childbirth journeys during the pandemic were reported as having positive and negative experiences which would counteract one-another. Lack of relational care, denial of embodied experiences, and removal from support networks were counterbalanced by good practice which persisted, understanding staff were trying to keep everyone safe, and renewed importance in the family unit. Conclusion Pregnancy can be an uncertain time for women. This was compounded by having to navigate their maternity journey alone during the COVID-19 pandemic.

Background Twenty percent of women in the UK develop perinatal mental health (PMH) problems, which have widespread effects on maternal and child health. Community pharmacists are ideally placed to identify PMH problems and refer to other trained healthcare professionals. Objective This study explored community pharmacists’ attitudes, current counselling practices, and barriers to providing mental health advice to perinatal women. Methods A qualitative focus group study was performed virtually with community pharmacists (n = 11), working in urban settings across London. A topic guide was used to cover current counselling practice, barriers to and confidence in counselling women, and thoughts on potential pharmacist-led perinatal mental health services. The focus groups were recorded, transcribed, and analysed using thematic analysis. Results Three themes were identified: Doing Mental Health Care; Willing, but Unable; and Introspection and reflection, which were related through a central organising concept of ‘Perinatal mental health care as a new frontier for community pharmacy’. It was found that while community pharmacists provide mental health advice to perinatal women and their partners, they lacked confidence, which was related to a lack of knowledge and inadequate training opportunities. Organisational barriers were identified including a lack of a formal referral pathway to existing mental health services and other trained healthcare professionals. Perceptions of opportunities and recommendations for service improvement and change were also garnered. Conclusion This study demonstrates community pharmacists have a potential role within community mental healthcare in identification of PMH problems and providing appropriate advice and support. Upskilling community pharmacists in mental health should be considered to increase knowledge and confidence while formal referral pathways to other trained healthcare professionals and existing services should be established and made available to pharmacists.

This paper investigates configuration switch and path selection of novel reconfigurable parallel mechanisms with two double-four-bar modular linkages in terms of subgroups SE(2), SO(3) and X(z). The motion representation of reconfigurable parallel mechanisms with three motion branches is proposed based on intersection operation of manifold generated, and the switching principle of motion generators is presented to realize the switching of the three motion branches of the reconfigurable parallel mechanism through the transformation of the submanifold generated by the suitable common motion generators. Two double-four-bar modular linkages are designed to constitute a subchain in terms of the switching principle, and the configuration transformation of the subchain is proposed with respects to the configuration switch of each modular linkage following different forms of the quotient submanifold generated. A reconfigurable parallel mechanism is synthesized by means of rearranging the configurations of two modular linkages of three identical subchains. Especially, the paths of three configurations of a reconfigurable parallel mechanism are selected to satisfy switching.

This study examined how inward foreign direct investment (IFDI) concentration affects the research and development (R&D) strategies of locally domiciled firms operating in emerging markets. From a resource dependence perspective, we argued that any community-specific interdependencies between local and foreign firms stimulate the former to engage in R&D activities. The findings of our analyses of panel data of 161,632 manufacturing firms across 525 four-digit-coded industries operating in China support our predictions that the R&D intensity of local firms responds positively to the presence of IFDI in competitive and symbiotic communities. In addition, the positive effects of IFDI on the level of R&D intensity of locally domiciled firms in competitive and symbiotic communities are enhanced by the foreign ownership of such firms. We conclude this paper by drawing the implications of our findings for theory and practice.