Threats, media coverage and public perceptions of foreign nations in Japan

Overall, this study finds evidence that Japanese Public opinion is stable over long periods of time and, although abrupt changes do occur, they tend to be small in magnitude, short-term and are associated mainly with those issues and events perceived as threats. This corresponds with the findings of researchers in the United States who have found that public opinion about foreign policy is relatively rational

Fabrication of free standing collagen membranes by pulsed-electrophoretic deposition.

This work reports an important new development in the production of collagen membranes, based on pulsed electrophoretic deposition (P-EPD), suitable for a wide range of biomedical applications. Collagen membranes are of great interest as a biomaterial and in a range of other industries, though current production techniques suffer from limitations with scaling up, homogeneity, and complex shapes. P-EPD can be used to rapidly create detachable, large-area, homogeneous products with controlled thickness in a wide variety of shapes. We provide a new understanding of the influence of a range of parameters (pulse width, voltage, duty cycle, solvent additions) and their effects on membrane structure. Characterisation by AFM, SEM, and cryoSEM revealed the ability to produce dense, structurally defect-free membranes, and significantly, we show and discuss the ability to produce thicker membranes by sequential deposition without seeing a corresponding increase in cell electrical resistance. We anticipate this novel, rapid, and controllable method for the production of collagen membranes to be of interest for a wide range of fields.The authors wish to acknowledge the support of theEngineering and Physical Sciences Research Council(EPSRC)grants EP/K503009/1, EP/J500380/1, EP/L504920/1, EP/M506485/1, and EP/M508007/1,Geistlich Pharma AG, and the European ResearchCouncil(ERC)Advanced Grant 320598 3D-

"The Mystery of the Raddlesham Mumps": A case study for combined storytelling in a theatre play and Virtual Reality

“The Mystery of the Raddlesham Mumps” is a poem by Murray Lachlan Young, aimed at both children and adults. This poem has been adapted as a theatre play with a short prequel as a Virtual Reality (VR)/tablet app. We used this unique combination to explore the potential interaction between these different media elements for the level of “presence” and “immersion” in the story (i.e. the level to which one can imagine oneself within the story at the expense of the sense of physical time and space). The theatre audience had the opportunity to play the VR/tablet app in the foyer before the performance started. After the performance, a questionnaire measured participants’ level of immersion and presence in the theatre play and their enjoyment of both play and app. The results showed that people of all ages interacted with and liked the app. Ratings for the play were also high and did not depend on prior engagement with the app. However, the play was liked more by adults than children, and the reverse was true for the app, suggesting a potential generation shift in multimedia story telling

“The Mystery of the Raddlesham Mumps”: a Case Study for Combined Storytelling in a Theatre Play and Virtual Reality

“The Mystery of the Raddlesham Mumps” is a poem by Murray Lachlan Young, aimed at both children and adults. This poem has been adapted as a theatre play with a short prequel as a Virtual Reality (VR) / tablet app. We used this unique combination to explore the potential interaction between these different media elements for the level of “presence” and “immersion” in the story (i.e. the level to which one can imagine oneself within the story at the expense of the sense of physical time and space). The theatre audience had the opportunity to play the VR / tablet app in the foyer before the performance started. After the performance, a questionnaire measured participants' level of immersion and presence in the theatre play and their enjoyment of both play and app. The results showed that people of all ages interacted with and liked the app. Ratings for the play were also high and did not depend on prior engagement with the app. However, the play was liked more by adults than children, and the reverse was true for the app, suggesting a potential generation shift in multimedia story telling

Community seroprevalence of SARS-CoV-2 in children and adolescents in England, 2019–2021

Objective: To understand community seroprevalence of SARS-CoV-2 in children and adolescents. This is vital to understanding the susceptibility of this cohort to COVID-19 and to inform public health policy for disease control such as immunisation. Design: We conducted a community-based cross-sectional seroprevalence study in participants aged 0–18 years old recruiting from seven regions in England between October 2019 and June 2021 and collecting extensive demographic and symptom data. Serum samples were tested for antibodies against SARS-CoV-2 spike and nucleocapsid proteins using Roche assays processed at UK Health Security Agency laboratories. Prevalence estimates were calculated for six time periods and were standardised by age group, ethnicity and National Health Service region. Results: Post-first wave (June–August 2020), the (anti-spike IgG) adjusted seroprevalence was 5.2%, varying from 0.9% (participants 10–14 years old) to 9.5% (participants 5–9 years old). By April–June 2021, this had increased to 19.9%, varying from 13.9% (participants 0–4 years old) to 32.7% (participants 15–18 years old). Minority ethnic groups had higher risk of SARS-CoV-2 seropositivity than white participants (OR 1.4, 95% CI 1.0 to 2.0), after adjusting for sex, age, region, time period, deprivation and urban/rural geography. In children <10 years, there were no symptoms or symptom clusters that reliably predicted seropositivity. Overall, 48% of seropositive participants with complete questionnaire data recalled no symptoms between February 2020 and their study visit. Conclusions: Approximately one-third of participants aged 15–18 years old had evidence of antibodies against SARS-CoV-2 prior to the introduction of widespread vaccination. These data demonstrate that ethnic background is independently associated with risk of SARS-CoV-2 infection in children. Trial registration number: NCT04061382

Depression and anxiety symptoms post-stroke/TIA:prevalence and associations in cross-sectional data from a regional stroke registry

BACKGROUND: Mood disorders are commonly seen in those with cerebrovascular disease. Literature to-date has tended to focus on depression and on patients with stroke, with relatively little known about post-stroke anxiety or mood disorder in those with transient ischaemic attack (TIA). We aimed to describe prevalence of depression and anxiety symptoms in stroke and TIA cohorts and to explore association with clinical and socio-demographic factors. METHODS: We used a city wide primary care stroke registry (Glasgow Local Enhanced Service for Stroke - LES). All community dwelling stroke-survivors were included. We described cross-sectional prevalence of depression and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS). Data on clinical and demographic details was collected and univariable and multivariable analyses performed to describe associations with HADS scores. We examined those with a diagnosis of 'stroke' and 'TIA' as separate cohorts. RESULTS: From 13,283 potentially eligible stroke patients in the registry, we had full HADS data on 4,079. Of the 3,584 potentially eligible TIA patients, we had full HADS data on 1,247 patients. Across the stroke cohort, 1181 (29%) had HADS anxiety scores suggestive of probable or possible anxiety; 993 (24%) for depression. For TIA patients, 361 (29%) had anxiety and 254 (21%) had depression. Independent predictors of both depression and anxiety symptoms were female sex, younger age and higher socioeconomic deprivation score (all p < 0.001). CONCLUSION: Using HADS, we found a high prevalence of anxiety and depression symptoms in a community-based cohort of patients with cerebrovascular disease

Serum HCoV-spike specific antibodies do not protect against subsequent SARS-CoV-2 infection in children and adolescents

SARS-CoV-2 infections in children are generally asymptomatic or mild and rarely progress to severe disease and hospitalization. Why this is so remains unclear. Here we explore the potential for protection due to pre-existing cross-reactive seasonal coronavirus antibodies and compare the rate of antibody decline for nucleocapsid and spike protein in serum and oral fluid against SARS-CoV-2 within the pediatric population. No differences in seasonal coronaviruses antibody concentrations were found at baseline between cases and controls, suggesting no protective effect from pre-existing immunity against seasonal coronaviruses. Antibodies against seasonal betacoronaviruses were boosted in response to SARS-CoV-2 infection. In serum, anti-nucleocapsid antibodies fell below the threshold of positivity more quickly than anti-spike protein antibodies. These findings add to our understanding of protection against infection with SARS-CoV-2 within the pediatric population, which is important when considering pediatric SARS-CoV-2 immunization policies

Accuracy of UK Rapid Test Consortium (UK-RTC) “AbC-19 Rapid Test” for detection of previous SARS-CoV-2 infection in key workers: test accuracy study

Abstract: Objective: To assess the accuracy of the AbC-19 Rapid Test lateral flow immunoassay for the detection of previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design: Test accuracy study. Setting: Laboratory based evaluation. Participants: 2847 key workers (healthcare staff, fire and rescue officers, and police officers) in England in June 2020 (268 with a previous polymerase chain reaction (PCR) positive result (median 63 days previously), 2579 with unknown previous infection status); and 1995 pre-pandemic blood donors. Main outcome measures: AbC-19 sensitivity and specificity, estimated using known negative (pre-pandemic) and known positive (PCR confirmed) samples as reference standards and secondly using the Roche Elecsys anti-nucleoprotein assay, a highly sensitive laboratory immunoassay, as a reference standard in samples from key workers. Results: Test result bands were often weak, with positive/negative discordance by three trained laboratory staff for 3.9% of devices. Using consensus readings, for known positive and negative samples sensitivity was 92.5% (95% confidence interval 88.8% to 95.1%) and specificity was 97.9% (97.2% to 98.4%). Using an immunoassay reference standard, sensitivity was 94.2% (90.7% to 96.5%) among PCR confirmed cases but 84.7% (80.6% to 88.1%) among other people with antibodies. This is consistent with AbC-19 being more sensitive when antibody concentrations are higher, as people with PCR confirmation tended to have more severe disease whereas only 62% (218/354) of seropositive participants had had symptoms. If 1 million key workers were tested with AbC-19 and 10% had actually been previously infected, 84 700 true positive and 18 900 false positive results would be projected. The probability that a positive result was correct would be 81.7% (76.8% to 85.8%). Conclusions: AbC-19 sensitivity was lower among unselected populations than among PCR confirmed cases of SARS-CoV-2, highlighting the scope for overestimation of assay performance in studies involving only PCR confirmed cases, owing to “spectrum bias.” Assuming that 10% of the tested population have had SARS-CoV-2 infection, around one in five key workers testing positive with AbC-19 would be false positives. Study registration: ISRCTN 56609224

Mechanisms of Resistance to Noncovalent Bruton's Tyrosine Kinase Inhibitors

BackgroundCovalent (irreversible) Bruton's tyrosine kinase (BTK) inhibitors have transformed the treatment of multiple B-cell cancers, especially chronic lymphocytic leukemia (CLL). However, resistance can arise through multiple mechanisms, including acquired mutations in BTK at residue C481, the binding site of covalent BTK inhibitors. Noncovalent (reversible) BTK inhibitors overcome this mechanism and other sources of resistance, but the mechanisms of resistance to these therapies are currently not well understood.MethodsWe performed genomic analyses of pretreatment specimens as well as specimens obtained at the time of disease progression from patients with CLL who had been treated with the noncovalent BTK inhibitor pirtobrutinib. Structural modeling, BTK-binding assays, and cell-based assays were conducted to study mutations that confer resistance to noncovalent BTK inhibitors.ResultsAmong 55 treated patients, we identified 9 patients with relapsed or refractory CLL and acquired mechanisms of genetic resistance to pirtobrutinib. We found mutations (V416L, A428D, M437R, T474I, and L528W) that were clustered in the kinase domain of BTK and that conferred resistance to both noncovalent BTK inhibitors and certain covalent BTK inhibitors. Mutations in BTK or phospholipase C gamma 2 (PLCγ2), a signaling molecule and downstream substrate of BTK, were found in all 9 patients. Transcriptional activation reflecting B-cell-receptor signaling persisted despite continued therapy with noncovalent BTK inhibitors.ConclusionsResistance to noncovalent BTK inhibitors arose through on-target BTK mutations and downstream PLCγ2 mutations that allowed escape from BTK inhibition. A proportion of these mutations also conferred resistance across clinically approved covalent BTK inhibitors. These data suggested new mechanisms of genomic escape from established covalent and novel noncovalent BTK inhibitors. (Funded by the American Society of Hematology and others.)

Optimisation of Collagen Films Produced via Pulsed Current Electrophoretic Deposition

Electrophoretic deposition (EPD) has been used for the deposition of insoluble collagen type I in aqueous suspensions. In this process, two electrodes are immersed in an aqueous collagen suspension and a voltage is applied. The charged particles in the suspension move towards the oppositely-charged electrode resulting in the deposition of a coating, which can be removed to create a free-standing collagen film. The aim of this project was to maximise processing efficiency and yield, and improve material properties of the collagen films produced using EPD. The behaviour of collagen I from two different suppliers was compared when processed using pulsed current electrophoretic deposition (PC-EPD). It was found that, at voltages required for adequate yield (at least 5 V), formation of bubbles or corrosion of the electrode occurred for suspensions in aqueous media. However, dialysis of collagen suspensions against deionised water for 30 hours was shown to remove residual charge-carrying ions, notably Na+, K+, Cl- and Ca2+, arising from the collagen extraction process. This allowed deposition to be carried out at higher voltages (up to 10 V), leading to higher yield and the production of consistent films, avoiding the processing problems. PC-EPD was mathematically modelled, in order to broaden understanding of the process and aid in future investigations. A pulsed current factor was developed and introduced to previously-described direct current EPD models, derived from the Hamaker equation. To validate this, collagen suspensions were characterised, and measured variables were implemented within the model. The model was compared with experimental data and was found to be accurate at applied potentials of 10 V and above. Deviations between the model and experimental values for voltages of 5 V or less were explained by factors within the pulse cycle that were not accounted for, such as molecule acceleration time. Collagen deposits, once dried, adhered strongly to the electrode and made removal from the substrate challenging. To solve this problem, a sacrificial cellulose acetate layer was developed to assist detachment of collagen deposits from the substrate, giving free- standing films. It was also shown that more complex collagen films could be created by depositing onto shaped electrodes, and that these could also be removed successfully using a cellulose sacrificial layer. Analysis of grooved films showed that features from the substrate were reproduced successfully onto the collagen deposits, with a resolution of 10 μm for topographical surface features, however, the larger grooved features measured approximately 100 μm (±50 μm) greater than the substrate due to the film thickness. The density of collagen biomaterials can influence their stability and degradation properties. The densities of cast films and EPD films were compared, and deposited films were found to be at least 15% more dense. Furthermore, it was found that the density of EPD collagen films could be controlled by changing the deposition voltage, with a densities ranging from 400 kg m−3 at 5 V to 700 kg m−3 at 10 V. Films with a higher density were shown to have increased enzymatic degradation resistance, potentially reducing the need for chemical cross-linkers to stabilise these collagen devices, giving potential benefits for bioactivity. Surgical application of membranes often requires the use of suturing and, therefore, the biomaterials are required to be tear-resistant. It was hypothesised that alignment of collagen fibres within the membranes would increase their ultimate tensile strength (UTS). Through optimisation of the EPD rig and processing parameters, alignment of collagen was induced during deposition by generating interfacial shear between the substrate and suspension. This was achieved using two different EPD setups, and the collagen alignment created was assessed using birefringence measurements. It was found that successful alignment was achieved (with corresponding birefringence values of 0.0025) using (1) a rotating cylindrical electrode with a tangential velocity of 0.0006 m s−1 at 10 V PC-EPD, and (2) volumetric flow rate of suspension pumped through the EPD cell of 1.67 mL s−1 at 40 V direct current EPD. This alignment was found to increase the UTS of cross-linked collagen films in the direction of alignment to 6.26 MPa, compared to 3.5 MPa in non-aligned films. Multilayer, cross-ply films were then produced by changing the film orientation between deposition steps. The development of the multi-orientated cross-ply collagen films could result in membranes with increased tear resistance. This thesis has developed the capabilities of EPD processing for collagen films, providing tunability of material properties and forms, and allowing for the design of collagen membranes for a range of medical applications.EPSRC studentship, the Geistlich Pharma AG sponsorship, EPSRC Impact Acceleration Account Follow-On Fund, and EPSRC Established Career fellowship Grant No EP/N019938/1