Feasibility of diffusion-tensor and correlated diffusion imaging for studying white-matter microstructural abnormalities: Application in COVID-19.

There has been growing attention on the effect of COVID-19 on white-matter microstructure, especially among those that self-isolated after being infected. There is also immense scientific interest and potential clinical utility to evaluate the sensitivity of single-shell diffusion magnetic resonance imaging (MRI) methods for detecting such effects. In this work, the performances of three single-shell-compatible diffusion MRI modeling methods are compared for detecting the effect of COVID-19, including diffusion-tensor imaging, diffusion-tensor decomposition of orthogonal moments and correlated diffusion imaging. Imaging was performed on self-isolated patients at the study initiation and 3-month follow-up, along with age- and sex-matched controls. We demonstrate through simulations and experimental data that correlated diffusion imaging is associated with far greater sensitivity, being the only one of the three single-shell methods to demonstrate COVID-19-related brain effects. Results suggest less restricted diffusion in the frontal lobe in COVID-19 patients, but also more restricted diffusion in the cerebellar white matter, in agreement with several existing studies highlighting the vulnerability of the cerebellum to COVID-19 infection. These results, taken together with the simulation results, suggest that a significant proportion of COVID-19 related white-matter microstructural pathology manifests as a change in tissue diffusivity. Interestingly, different b-values also confer different sensitivities to the effects. No significant difference was observed in patients at the 3-month follow-up, likely due to the limited size of the follow-up cohort. To summarize, correlated diffusion imaging is shown to be a viable single-shell diffusion analysis approach that allows us to uncover opposing patterns of diffusion changes in the frontal and cerebellar regions of COVID-19 patients, suggesting the two regions react differently to viral infection.

Effects of post-acute COVID-19 syndrome on the functional brain networks of non-hospitalized individuals.

Introduction: The long-term impact of COVID-19 on brain function remains poorly understood, despite growing concern surrounding post-acute COVID-19 syndrome (PACS). The goal of this cross-sectional, observational study was to determine whether there are significant alterations in resting brain function among non-hospitalized individuals with PACS, compared to symptomatic individuals with non-COVID infection. Methods: Data were collected for 51 individuals who tested positive for COVID-19 (mean age 41±12 yrs., 34 female) and 15 controls who had cold and flu-like symptoms but tested negative for COVID-19 (mean age 41±14 yrs., 9 female), with both groups assessed an average of 4-5 months after COVID testing. None of the participants had prior neurologic, psychiatric, or cardiovascular illness. Resting brain function was assessed via functional magnetic resonance imaging (fMRI), and self-reported symptoms were recorded. Results: Individuals with COVID-19 had lower temporal and subcortical functional connectivity relative to controls. A greater number of ongoing post-COVID symptoms was also associated with altered functional connectivity between temporal, parietal, occipital and subcortical regions. Discussion: These results provide preliminary evidence that patterns of functional connectivity distinguish PACS from non-COVID infection and correlate with the severity of clinical outcome, providing novel insights into this highly prevalent disorder.

A tale of three pandemics: Shining a light on a hidden problem.

An "epidemic" is an event in which a disease, infectious or non-infectious, is actively spreading within a population and designated area. The term "pandemic" is defined as "an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and usually affecting a large number of people". The global response to the COVID-19 pandemic has not been seen since the outbreak of Human Immunodeficiency Virus in the early eighties. But there is another unseen pandemic running alongside the current COVID-19 pandemic, which affects a vast number of people, crossing international boundaries and occurring in every single country worldwide. The pandemic of traumatic injuries. Traumatic injuries account for 11% of the current Global Burden of Disease, resulting in nearly 5 million deaths annually and is the third-leading cause of death worldwide. For every trauma-related death, it is estimated that up to 50 people sustain permanent or temporary disabilities. Furthermore, traumatic injuries occur at disproportionately higher rates in low- and middle-income countries, with approximately 90% of injuries and more than 90% of global deaths from injury occurring these countries. Injuries are increasing worldwide, crossing international boundaries and affecting a large number of people, in the same manner Human Immunodeficiency Virus did in the 1980's and COVID-19 is today. The tremendous global effort to tackle the COVID-19 and Human Immunodeficiency Virus pandemics has occurred whilst ignoring the comparable pandemic of injury. Without change and future engagement with policy makers and international donors this disparity is likely to continue.

Key features of a trauma-informed public health emergency approach: A rapid review.

COVID-19 is a major threat to public safety, and emergency public health measures to protect lives (e.g., lockdown, social distancing) have caused widespread disruption. While these measures are necessary to prevent catastrophic trauma and grief, many people are experiencing heightened stress and fear. Public health measures, risks of COVID-19 and stress responses compound existing inequities in our community. First Nations communities are particularly at risk due to historical trauma, ongoing socio-economic deprivation, and lack of trust in government authorities as a result of colonization. The objective of this study was to review evidence for trauma-informed public health emergency responses to inform development of a culturally-responsive trauma-informed public health emergency framework for First Nations communities. We searched relevant databases from 1/1/2000 to 13/11/2020 inclusive, which identified 40 primary studies (and eight associated references) for inclusion in this review. Extracted data were subjected to framework and thematic synthesis. No studies reported evaluations of a trauma-informed public health emergency response. However, included studies highlighted key elements of a "trauma-informed lens," which may help to consider implications, reduce risks and foster a sense of security, wellbeing, self- and collective-efficacy, hope and resilience for First Nations communities during COVID-19. We identified key elements for minimizing the impact of compounding trauma on First Nations communities, including: a commitment to equity and human rights, cultural responsiveness, good communication, and positive leadership. The six principles guiding trauma-informed culturally-responsive public health emergency frameworks included: (i) safety, (ii) empowerment, (iii) holistic support, (iv) connectedness and collaboration, (v) compassion and caring, and (vi) trust and transparency in multi-level responses, well-functioning social systems, and provision of basic services. These findings will be discussed with First Nations public health experts, together with data on the experiences of First Nations families and communities during COVID-19, to develop a trauma-integrated public health emergency response framework or "lens" to minimize compounding trauma for First Nations communities.

"You Can't Replace That Feeling of Connection to Culture and Country": Aboriginal and Torres Strait Islander Parents' Experiences of the COVID-19 Pandemic.

This Aboriginal-led study explores Aboriginal and Torres Strait Islander parents' experiences of COVID-19. 110 Aboriginal and Torres Strait Islander parents were interviewed between October 2020 and March 2022. Participants were recruited through community networks and partner health services in South Australia, Victoria, and Northern Territory, Australia. Participants were predominantly female (89%) and based in Victoria (47%) or South Australia (45%). Inductive thematic analysis identified three themes: (1) Changes to daily living; (2) Impact on social and emotional wellbeing; and (3) Disconnection from family, community, and culture. COVID-19 impacted Aboriginal and Torres Strait Islander families. Disruption to cultural practice, and disconnection from country, family, and community was detrimental to wellbeing. These impacts aggravated pre-existing inequalities and may continue to have greater impact on Aboriginal and Torres Strait Islander parents and communities due to intergenerational trauma, stemming from colonisation, violence and dispossession and ongoing systemic racism. We advocate for the development of a framework that ensures an equitable approach to future public health responses for Aboriginal and Torres Strait Islander people.

MRI Assessment of Cerebral Blood Flow in Nonhospitalized Adults Who Self-Isolated Due to COVID-19.

BACKGROUND: Neurological symptoms associated with coronavirus disease 2019 (COVID-19), such as fatigue and smell/taste changes, persist beyond infection. However, little is known of brain physiology in the post-COVID-19 timeframe. PURPOSE: To determine whether adults who experienced flu-like symptoms due to COVID-19 would exhibit cerebral blood flow (CBF) alterations in the weeks/months beyond infection, relative to controls who experienced flu-like symptoms but tested negative for COVID-19. STUDY TYPE: Prospective observational. POPULATION: A total of 39 adults who previously self-isolated at home due to COVID-19 (41.9 ± 12.6 years of age, 59% female, 116.5 ± 62.2 days since positive diagnosis) and 11 controls who experienced flu-like symptoms but had a negative COVID-19 diagnosis (41.5 ± 13.4 years of age, 55% female, 112.1 ± 59.5 since negative diagnosis). FIELD STRENGTH AND SEQUENCES: A 3.0 T; T1-weighted magnetization-prepared rapid gradient and echo-planar turbo gradient-spin echo arterial spin labeling sequences. ASSESSMENT: Arterial spin labeling was used to estimate CBF. A self-reported questionnaire assessed symptoms, including ongoing fatigue. CBF was compared between COVID-19 and control groups and between those with (n = 11) and without self-reported ongoing fatigue (n = 28) within the COVID-19 group. STATISTICAL TESTS: Between-group and within-group comparisons of CBF were performed in a voxel-wise manner, controlling for age and sex, at a family-wise error rate of 0.05. RESULTS: Relative to controls, the COVID-19 group exhibited significantly decreased CBF in subcortical regions including the thalamus, orbitofrontal cortex, and basal ganglia (maximum cluster size = 6012 voxels and maximum t-statistic = 5.21). Within the COVID-19 group, significant CBF differences in occipital and parietal regions were observed between those with and without self-reported on-going fatigue. DATA CONCLUSION: These cross-sectional data revealed regional CBF decreases in the COVID-19 group, suggesting the relevance of brain physiology in the post-COVID-19 timeframe. This research may help elucidate the heterogeneous symptoms of the post-COVID-19 condition. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.

A Culturally Responsive Trauma-Informed Public Health Emergency Framework for Aboriginal and Torres Strait Islander Communities in Australia, Developed during COVID-19.

The Coronavirus Disease 2019 (COVID-19) pandemic impacted peoples' livelihoods and mental wellbeing. Aboriginal and Torres Strait Islander peoples in Australia continue to experience intergenerational trauma associated with colonization and may experience trauma-related distress in response to government responses to public health emergencies. We aimed to develop a culturally responsive trauma-informed public health emergency response framework for Aboriginal and Torres Strait Islander peoples. This Aboriginal and Torres Strait Islander-led study involved: (i) a review of trauma-informed public health emergency responses to develop a draft framework (ii) interviews with 110 Aboriginal and Torres Strait Islander parents about how COVID-19 impacted their lives, and (iii) a workshop with 36 stakeholders about pandemic experiences using framework analysis to refine a culturally responsive trauma-informed framework. The framework included: an overarching philosophy (cultural humility, safety and responsiveness); key enablers (local leadership and Eldership); supporting strategies (provision of basic needs and resources, well-functioning social systems, human rights, dignity, choice, justice and ethics, mutuality and collective responsibility, and strengthening of existing systems); interdependent core concepts (safety, transparency, and empowerment, holistic support, connectedness and collaboration, and compassion, protection and caring); and central goals (a sense of security, resilience, wellbeing, self- and collective-efficacy, hope, trust, resilience, and healing from grief and loss).

Aboriginal peoples' perspectives about COVID-19 vaccines and motivations to seek vaccination: a qualitative study.

INTRODUCTION: Aboriginal and Torres Strait Islander (Aboriginal) people compared with non-Aboriginal people in Australia have higher rates of chronic conditions. These conditions increase the risk of poorer health outcomes if infected with COVID-19, highlighting the importance of COVID-19 vaccination. This study examined what Aboriginal people think about COVID-19 vaccines, reasons why they were vaccinated or not vaccinated and factors involved in receiving COVID-19 vaccination. METHODS: We used a participatory peer researcher method to interview 35 Aboriginal people aged 15-80 years living in Western Sydney, Australia. Local Aboriginal people who had ties with the community conducted the interviews. The questions and analyses were framed using the WHO's Behavioural and Social Drivers of COVID-19 model. Interviews occurred between February 2021 and March 2021. Peer researchers were paid for their time in training and to conduct the interviews and each participant received $50. RESULTS: Reasons why participants would seek vaccination included: to protect themselves from infection and severe illness, to protect others in their community, to travel again and to return to 'normal life'. Reasons why some participants were hesitant about being vaccinated included: fear of vaccine side effects; negative stories on social media; and distrust in Australian governments and medical institutions. Aboriginal people preferred to access COVID-19 vaccination through their local Aboriginal Health Service or a general practitioner they already knew. CONCLUSION: Achieving high vaccination rates in Aboriginal communities is possible if vaccination programmes are delivered through trusted general practitioners or Aboriginal Health Services.

The pig as an amplifying host for new and emerging zoonotic viruses.

Pig production is a rapidly growing segment of the global livestock sector, especially in Asia and Africa. Expansion and intensification of pig production has resulted in significant changes to traditional pig husbandry practices leading to an environment conducive to increased emergence and spread of infectious diseases. These include a number of zoonotic viruses including influenza, Japanese encephalitis, Nipah and coronaviruses. Pigs are known to independently facilitate the creation of novel reassortant influenza A virus strains, capable of causing pandemics. Moreover, pigs play a role in the amplification of Japanese encephalitis virus, transmitted by mosquito vectors found in areas inhabited by over half the world's human population. Furthermore, pigs acted as an amplifying host in the first and still most severe outbreak of Nipah virus in Malaysia, that necessitated the culling over 1 million pigs. Finally, novel porcine coronaviruses are being discovered in high pig-density countries which have pandemic potential. In this review, we discuss the role that pigs play as intermediate/amplifying hosts for zoonotic viruses with pandemic potential and consider how multivalent vaccination of pigs could in turn safeguard human health.

An evaluation of the incorporation of psychological interventions into the care of patients with a diagnosis of emotionally unstable personality disorder following admission to the general adult inpatient setting

Aims To assess incorporation of and access to psychological therapies for patients with a diagnosis of emotionally unstable personality (EUPD) who were discharged from the inpatient wards at Clock View Hospital, an inpatient unit in Mersey Care NHS Foundation Trust. Method A retrospective analysis of the electronic record of 50 patients discharged from Clock View Hospital between 1st of January 2020 and 1st of November 2020 was performed to assess whether patients were engaged with psychotherapy and whether they had an extended care plan in place. 25 patients with EUPD and no associated psychiatric comorbidities were included in the sample, as well as 25 patients with EUPD and associated psychiatric comorbidities. Result Those EUPD patients with no psychiatric comorbidities were more likely to be under the care of the Liverpool Personality Disorder (PD) Hub compared to those with psychiatric comorbidities (12 vs seven patients). Of the 19 patients under the PD Hub, 11 had a Case Manager, four were engaged with the PD Hub's day services / safe service and one with a PD Hub readiness group. Six of the 50 patients had a documented refusal to engage with the PD Hub. Only 27 of the patients had either received psychological intervention, were on a waiting list, or had a referral in place. 16% of patients refused a psychotherapy referral. Of the 20 patients who received psychological treatment, eight completed a form of psychotherapy (cognitive analytic therapy, dialectical behaviour therapy, cognitive behavioural therapy, eye movement desensitisation and reprocessing) and 12 psychological intervention (either structured case management, psychoeducation or emotional coping skills). Only 28 of 50 patients had an extended care plan and 28 had a collaborative risk management plan in place. Conclusion There was no obvious correlation between previous completion of psychological therapy and degree of polypharmacy. Median admission time was reduced for patients under the PD Hub (six vs 14 days). This was also reduced for patients who accessed psychotherapy or psychotherapeutic interventions (nine vs 10 days). This audit coincided with the COVID-19 pandemic and subsequent reduced access to the PD Hub and psychotherapy service. There is a need to consider barriers to EUPD patients receiving psychotherapy. EUPD patients may have numerous hospital admissions and frequently present in crisis. Given the iatrogenic harm from prolonged hospital admission, there is a need to consider incorporating a collaborative extended care plan and risk management plan as part of discharge planning, following admission to hospital.

Brain structure and function in people recovering from COVID-19 after hospital discharge or self-isolation: a longitudinal observational study protocol.

BACKGROUND: The detailed extent of neuroinvasion or deleterious brain changes resulting from COVID-19 and their time courses remain to be determined in relation to "long-haul" COVID-19 symptoms. Our objective is to determine whether there are alterations in functional brain imaging measures among people with COVID-19 after hospital discharge or self-isolation. METHODS: This paper describes a protocol for NeuroCOVID-19, a longitudinal observational study of adults aged 20-75 years at Sunnybrook Health Sciences Centre in Toronto, Ontario, that began in April 2020. We aim to recruit 240 adults, 60 per group: people who contracted COVID-19 and were admitted to hospital (group 1), people who contracted COVID-19 and self-isolated (group 2), people who experienced influenza-like symptoms at acute presentation but tested negative for COVID-19 and self-isolated (group 3, control) and healthy people (group 4, control). Participants are excluded based on premorbid neurologic or severe psychiatric illness, unstable cardiovascular disease, and magnetic resonance imaging (MRI) contraindications. Initial and 3-month follow-up assessments include multiparametric brain MRI and electroencephalography. Sensation and cognition are assessed alongside neuropsychiatric assessments and symptom self-reports. We will test the data from the initial and follow-up assessments for group differences based on 3 outcome measures: MRI cerebral blood flow, MRI resting state fractional amplitude of low-frequency fluctuation and electroencephalography spectral power. INTERPRETATION: If neurophysiologic alterations are detected in the COVID-19 groups in our NeuroCOVID-19 study, this information could inform future research regarding interventions for long-haul COVID-19. The study results will be disseminated to scientists, clinicians and COVID-19 survivors, as well as the public and private sectors to provide context on how brain measures relate to lingering symptoms.

Combinatorial F-G Immunogens as Nipah and Respiratory Syncytial Virus Vaccine Candidates.

Nipah virus (NiV) and respiratory syncytial virus (RSV) possess two surface glycoproteins involved in cellular attachment and membrane fusion, both of which are potential targets for vaccines. The majority of vaccine development is focused on the attachment (G) protein of NiV, which is the immunodominant target. In contrast, the fusion (F) protein of RSV is the main target in vaccine development. Despite this, neutralising epitopes have been described in NiV F and RSV G, making them alternate targets for vaccine design. Through rational design, we have developed a vaccine strategy applicable to phylogenetically divergent NiV and RSV that comprises both the F and G proteins (FxG). In a mouse immunization model, we found that NiV FxG elicited an improved immune response capable of neutralising pseudotyped NiV and a NiV mutant that is able to escape neutralisation by two known F-specific antibodies. RSV FxG elicited an immune response against both F and G and was able to neutralise RSV; however, this was inferior to the immune response of F alone. Despite this, RSV FxG elicited a response against a known protective epitope within G that is conserved across RSV A and B subgroups, which may provide additional protection in vivo. We conclude that inclusion of F and G antigens within a single design provides a streamlined subunit vaccine strategy against both emerging and established pathogens, with the potential for broader protection against NiV.

The impact of COVID-19 on antipsychotic prescriptions for patients with schizophrenia in Australia.

OBJECTIVE: To assess the impact, in the Australian setting, of the COVID-19 lockdown on antipsychotic supplies for patients with schizophrenia following a prescription from a new medical consultation when compared to the same periods in the previous 4 years. A secondary objective was to assess the volume of all antipsychotic supplies, from new and repeat prescriptions, over these same periods. METHODS: A retrospective pharmaceutical claims database study was undertaken, using the Department of Human Services Pharmaceutical Benefits Scheme 10% sample. The study population included all adult patients with three or more supplies of oral or long-acting injectable antipsychotics for the treatment of schizophrenia at any time between 1 June 2015 and 31 May 2020. The primary outcome compared volumes of dispensed antipsychotics from new prescriptions (which require a medical consultation) between 1 April and 31 May each year from 2016 to 2020. This was to analyse the period during which the Australian Government imposed a lockdown due to COVID-19 (April to May 2020) when compared the same periods in previous years. RESULTS: There was a small (5.7%) reduction in the number of antipsychotics dispensed from new prescriptions requiring a consultation, from 15,244 to 14,372, between April and May 2019 and the same period in 2020, respectively. However, this reduction was not statistically significant (p = 0.75) after adjusting for treatment class, age, gender, location and provider type. CONCLUSION: The COVID-19 restrictions during April and May 2020 had no significant impact on the volume of antipsychotics dispensed from new prescriptions for patients with schizophrenia when compared to the volume of antipsychotics dispensed from new prescriptions during the same period in previous years.

Collaborative Overview of coronaVIrus impact on ORTHopaedic training in the UK (COVI - ORTH UK).

INTRODUCTION: COVID-19 was declared a pandemic by the World Health Organization on the 11th of March 2020 with the NHS deferring all non-urgent activity from the 15th of April 2020. The aim of our study was to assess the impact of COVID-19 on Trauma and Orthopaedic trainees nationally. METHODS: Trauma and Orthopaedic (T&O) specialty trainees nationally were asked to complete an electronic survey specifically on the impact of COVID-19 on their training. This UK based survey was conducted between May 2020 and July 2020. RESULTS: A total of 185 out of 975 (19%) T&O specialty trainees completed the survey. Redeployment was experienced by 25% of trainees. 84% of respondents had experienced a fall in total operating numbers in comparison with the same time period in 2019. 89% experienced a fall in elective operating and 63% experienced a fall in trauma operating. The pandemic has also had an effect on the delivery of teaching, with face to face teaching being replaced by webinar-based teaching. 63% of training programmes delivered regular weekly teaching, whilst 19% provided infrequent sessions and 11% provided no teaching. CONCLUSION: This study has objectively demonstrated the significant impact of the COVID-19 pandemic on all aspects of T&O training.

A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses.

There is need for effective and affordable vaccines against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a protein nanoparticle vaccine against SARS-CoV-2. The vaccine is based on the display of coronavirus spike glycoprotein receptor-binding domain (RBD) on a synthetic virus-like particle (VLP) platform, SpyCatcher003-mi3, using SpyTag/SpyCatcher technology. Low doses of RBD-SpyVLP in a prime-boost regimen induce a strong neutralising antibody response in mice and pigs that is superior to convalescent human sera. We evaluate antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we show that RBD-SpyVLP induces a polyclonal antibody response that recognises key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. Moreover, RBD-SpyVLP is thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence. The data suggests that RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic.

Micro-fusion inhibition tests: quantifying antibody neutralization of virus-mediated cell-cell fusion.

Although enveloped viruses canonically mediate particle entry through virus-cell fusion, certain viruses can spread by cell-cell fusion, brought about by receptor engagement and triggering of membrane-bound, viral-encoded fusion proteins on the surface of cells. The formation of pathogenic syncytia or multinucleated cells is seen in vivo, but their contribution to viral pathogenesis is poorly understood. For the negative-strand paramyxoviruses respiratory syncytial virus (RSV) and Nipah virus (NiV), cell-cell spread is highly efficient because their oligomeric fusion protein complexes are active at neutral pH. The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has also been reported to induce syncytia formation in infected cells, with the spike protein initiating cell-cell fusion. Whilst it is well established that fusion protein-specific antibodies can block particle attachment and/or entry into the cell (canonical virus neutralization), their capacity to inhibit cell-cell fusion and the consequences of this neutralization for the control of infection are not well characterized, in part because of the lack of specific tools to assay and quantify this activity. Using an adapted bimolecular fluorescence complementation assay, based on a split GFP-Renilla luciferase reporter, we have established a micro-fusion inhibition test (mFIT) that allows the identification and quantification of these neutralizing antibodies. This assay has been optimized for high-throughput use and its applicability has been demonstrated by screening monoclonal antibody (mAb)-mediated inhibition of RSV and NiV fusion and, separately, the development of fusion-inhibitory antibodies following NiV vaccine immunization in pigs. In light of the recent emergence of coronavirus disease 2019 (COVID-19), a similar assay was developed for SARS-CoV-2 and used to screen mAbs and convalescent patient plasma for fusion-inhibitory antibodies. Using mFITs to assess antibody responses following natural infection or vaccination is favourable, as this assay can be performed entirely at low biocontainment, without the need for live virus. In addition, the repertoire of antibodies that inhibit cell-cell fusion may be different to those that inhibit particle entry, shedding light on the mechanisms underpinning antibody-mediated neutralization of viral spread.

Three-Tesla Magnetic Resonance Imaging of Patients With Deep Brain Stimulators: Results From a Phantom Study and a Pilot Study in Patients.

BACKGROUND: Deep brain stimulation (DBS) is a standard of care treatment for multiple neurologic disorders. Although 3-tesla (3T) magnetic resonance imaging (MRI) has become the gold-standard modality for structural and functional imaging, most centers refrain from 3T imaging in patients with DBS devices in place because of safety concerns. 3T MRI could be used not only for structural imaging, but also for functional MRI to study the effects of DBS on neurocircuitry and optimize programming. OBJECTIVE: To use an anthropomorphic phantom design to perform temperature and voltage safety testing on an activated DBS device during 3T imaging. METHODS: An anthropomorphic 3D-printed human phantom was constructed and used to perform temperature and voltage testing on a DBS device during 3T MRI. Based on the phantom assessment, a cohort study was conducted in which 6 human patients underwent MRI with their DBS device in an activated (ON) state. RESULTS: During the phantom study, temperature rises were under 2°C during all sequences, with the DBS in both the deactivated and activated states. Radiofrequency pulses from the MRI appeared to modulate the electrical discharge from the DBS, resulting in slight fluctuations of voltage amplitude. Six human subjects underwent MRI with their DBS in an activated state without any serious adverse events. One patient experienced stimulation-related side effects during T1-MPRAGE scanning with the DBS in an ON state because of radiofrequency-induced modulation of voltage amplitude. CONCLUSION: Following careful phantom-based safety testing, 3T structural and functional MRI can be safely performed in subjects with activated deep brain stimulators.

Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19.

Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Here, we compared the immunogenicity of one or two doses of ChAdOx1 nCoV-19 in both mice and pigs. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres.