Being cut off from social identity resources has shaped loneliness during the coronavirus pandemic: A longitudinal interview study with medically vulnerable older adults from the United Kingdom

Loneliness is a pernicious problem in older adulthood, associated with physical decline and isolation from valued social groups. However, the long‐term evolving experiences of ageing, identity and loneliness have yet to be elucidated. We use a Qualitative Longitudinal Research interview approach with nine vulnerable older adults (Agemean = 79.4 years), in which five participants were interviewed twice between 2019 and 2020, and four participants were interviewed at three‐time points from 2019 to 2021. This study aims to understand the unfolding experiences of ageing, social identity and loneliness during a prolonged period of social isolation during the Coronavirus pandemic. A theoretically guided thematic analysis highlights that participants initially experience ‘Categorisation as Vulnerable and Loss of Agency’ and ‘Shrinking Social Worlds’, leading to ‘Undermining of Reciprocal Support’ and ‘Fears of Persistent Loneliness’. Findings suggest that interventions to ameliorate loneliness among older adults would benefit from addressing age‐based stereotypes and emphasising the value of reciprocal contributions that older adults can make to their networks, as well as scaffolding and enhancing social identification with new groups. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

The fusion crust of the Winchcombe meteorite: a preserved record of atmospheric entry processes

Fusion crusts form during the atmospheric entry heating of meteorites and preserve a record of the conditions that occurred during deceleration in the atmosphere. The fusion crust of the Winchcombe meteorite closely resembles that of other stony meteorites, and in particular CM2 chondrites, since it is dominated by olivine phenocrysts set in a glassy mesostasis with magnetite, and is highly vesicular. Dehydration cracks are unusually abundant in Winchcombe. Failure of this weak layer is an additional ablation mechanism to produce large numbers of particles during deceleration, consistent with the observation of pulses of plasma in videos of the Winchcombe fireball. Calving events might provide an observable phenomenon related to meteorites that are particularly susceptible to dehydration. Oscillatory zoning is observed within olivine phenocrysts in the fusion crust, in contrast to other meteorites, perhaps owing to temperature fluctuations resulting from calving events. Magnetite monolayers are found in the crust, and have also not been previously reported, and form discontinuous strata. These features grade into magnetite rims formed on the external surface of the crust and suggest the trapping of surface magnetite by collapse of melt. Magnetite monolayers may be a feature of meteorites that undergo significant degassing. Silicate warts with dendritic textures were observed and are suggested to be droplets ablated from another stone in the shower. They, therefore, represent the first evidence for intershower transfer of ablation materials and are consistent with the other evidence in the Winchcombe meteorite for unusually intense gas loss and ablation, despite its low entry velocity.Science and Technology Facilities Council (STFC): ST/V000799/

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

WPI Combined Heat and Power Feasibility

We explored the potential use of combined heat and power (CHP) on the main campus of Worcester Polytechnic Institute. CHP units have the potential to reduce electricity and heating costs, while simultaneously lowering greenhouse gas emissions. We interviewed stakeholders to determine requirements, carried out a payback analysis, and estimated carbon waste savings. The team concluded that implementing a 2 megawatt reciprocating CHP unit would be best for campus

The effectiveness of self-guided virtual-reality exposure therapy for public-speaking anxiety

Objectives: Self-guided virtual-reality exposure therapy (VRET) is a psychological intervention that enables a person to increase their own exposure to perceived threat. Public-speaking anxiety (PSA) is an anxiety-provoking social situation that is characterized by fear of negative evaluation from an audience. This pilot study aimed to determine whether self-guided VRET (1) increases exposure to PSA-specific virtual social threats, and (2) reduces anxiety, arousal, heartrate and PSA over repeated exposure. Methods: Thirty-two University students (27 completers) with high self-reported public-speaking anxiety attended 2 weekly self-guided VRET sessions. Each session involved the participant delivering a 20-min speech in a virtual classroom. Participants were able to increase their exposure to virtual social threat through the audience size, audience reaction, number of speech prompts, and their own salience in the virtual classroom at 4-min intervals. Participants' heartrates and self-reported anxiety and arousal were monitored during these intervals. Participants completed psychometric assessments after each session and 1 month later. Results: Participants increased their exposure to virtual social threat during each VRET session, which coincided with a reduction in heartrate and self-reported anxiety and arousal. Improvement in PSA occurred post-treatment and 1 month later. The in-session improvement in anxiety correlated with reductions in fear of negative evaluation post-treatment and 1 month later. Conclusions: Increased self-exposure to virtual social threat from self-guided VRET relieves anxiety and shows immediate reductions in subjective and physiological arousal during application, but also yields sustained improvement in PSA

Being cut off from social identity resources has shaped loneliness during the Coronavirus pandemic: A longitudinal interview study with medically vulnerable older adults from the United Kingdom

Loneliness is a pernicious problem in older adulthood, associated with physical decline and isolation from valued social groups. However, the long-term evolving experiences of ageing, identity, and loneliness have yet to be elucidated. We use a Qualitative Longitudinal Research interview approach with nine vulnerable older adults (Agemean=79.4 years), in which five participants were interviewed twice between 2019 – 2020, and four participants were interviewed at three timepoints from 2019-2021. This study aims to understand unfolding experiences of ageing, social identity, and loneliness during a prolonged period of social isolation during the Coronavirus pandemic. A theoretically guided thematic analysis highlights that participants initially experience “Categorisation as Vulnerable and Loss of Agency” and “Shrinking Social Worlds”, leading to “Undermining of Reciprocal Support” and “Fears of Persistent Loneliness”. Findings suggest that interventions to ameliorate loneliness among older adults would benefit from addressing age-based stereotypes and emphasising the value of reciprocal contributions that older adults can make to their networks, as well as scaffolding and enhancing social identification with new groups