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Objective: The first COVID-19 pandemic wave was a period of reduced surgical activity and redistribution of resources to only those with late stage or critical presentations. This Vascular and Endovascular Research Network COVID-19 Vascular Service (COVER) study aimed to describe the six-month outcomes of patients who underwent open surgery and or endovascular interventions for major vascular conditions during this period. Methods: In this international, multicentre, prospective, observational study, centres recruited consecutive patients undergoing vascular procedures over a 12-week period. The study opened in March 2020 and closed to recruitment in August 2020. Patient demographics, procedure details, and post-operative outcomes were collected on a secure online database. The reported outcomes at 30 days and six months were post-operative complications, re-interventions, and all cause in-hospital mortality rate. Multivariable logistic regression was used to assess factors associated with six-month mortality rate. Results: Data were collected on 3 150 vascular procedures, including 1 380 lower limb revascularisations, 609 amputations, 403 aortic, 289 carotid, and 469 other vascular interventions. The median age was 68 years (interquartile range 59, 76), 73.5% were men, and 1.7% had confirmed COVID-19 disease. The cumulative all cause in-hospital, 30-day, and six-month mortality rates were 9.1%, 10.4%, and 12.8%, respectively. The six-month mortality rate was 32.1% (95% CI 24.2–40.8%) in patients with confirmed COVID-19 compared with 12.0% (95% CI 10.8–13.2%) in those without. After adjustment, confirmed COVID-19 was associated with a three times higher odds of six-month death (adjusted OR 3.25, 95% CI 2.18–4.83). Increasing ASA grade (3–5 vs. 1–2), frailty scores 4–9, diabetes mellitus, and urgent and or immediate procedures were also independently associated with increased odds of death by six months, while statin use had a protective effect. Conclusion: During the first wave of the pandemic, the six-month mortality rate after vascular and endovascular procedures was higher compared with historic pre-pandemic studies and associated with COVID-19 disease.

Achieving net zero by 2050 requires the decarbonisation of road transport. Electrification is recognised as a market-ready solution for certain transport segments, but it still poses a considerable challenge when applied to road freight. Any consensus on the technology choice for road freight electrification has still not been established. Embedding stakeholder input in the approach to address the technology adoption challenge has proven useful in uncovering various perspectives, which can provide useful insights into managing such transitions. This review paper hence took a three-step approach where the findings from the initial step of the literature search were taken up for the second step of stakeholder validation and feedback. The third step involved an analysis of the input gathered and the subsequent literature review to arrive at the conclusions. The outcome from the stakeholder engagement suggests that any specific technology can only support the transition to electrified road freight if enabled by system changes around policy, infrastructure, user behaviour, and the societal setup A follow-up literature review validated the need for a sociotechnical approach to such transitions where system changes are involved. The review also found gaps in the literature when it comes to embedding such sociotechnical approaches to technology adoption for road freight transport.

This paper documents part of the process of preparing to fully reopen the physical Self-Access Learning Center (SALC) in a university in Japan after being somewhat interrupted during two years of the COVID-19 pandemic. Self-access is becoming increasingly complex, multi-faceted and multi-disciplinary and it is necessary to revisit SALC mission statements periodically, particularly after major events or changes. A group of language educators working at the university examined literature and theories from a range of perspectives in order to inform the future directions of the SALC. In a series of meetings over a one-semester period, one or two team members led a guided discussion based on some key papers, talks or other resources related to eight themes. After a semester of such discussions, they returned to the mission statement and re-examined it, making it more theoretically robust and specific, acting as a guide for SALC services for a new era.

Abstract A coronavirus antigen microarray (COVAM) was constructed containing 11 SARS-CoV-2, 5 SARS-1, 5 MERS, and 12 seasonal coronavirus recombinant proteins. The array is designed to measure immunoglobulin isotype and subtype levels in serum or plasma samples against each of the individual antigens printed on the array. We probed the COVAM with COVID-19 convalescent plasma (CCP) collected from 99 donors who recovered from a PCR+ confirmed SARS-CoV-2 infection. The results were analyzed using two computational approaches, a generalized linear model (glm) and random forest (RF) prediction model, to classify individual specimens as either Reactive or non-reactive against the SARS-CoV-2 antigens. A training set of 88 pre-COVID-19 specimens (PreCoV) collected in August 2019 and102 positive specimens from SARS-CoV-2 PCR+ confirmed COVID-19 cases was used for these analyses. Results compared with an FDA emergency use authorized (EUA) SARS-CoV2 S1-based total Ig chemiluminescence immunoassay (Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 Total, CoV2T) and with a SARS-CoV-2 S1-S2 spike-based pseudovirus micro neutralization assay (SARS-CoV-2 reporter viral particle neutralization titration (RVPNT) showed high concordance between the three assays. Three CCP specimens that were negative by the VITROS CoV2T immunoassay were also negative by both COVAM and the RVPNT assay. Concordance between VITROS CoV2T and COVAM was 96%, VITROS CoV2T and RVPNT 93%, and RVPNT and COVAM 91%. The discordances were all weakly reactive samples near the cutoff threshold of the VITROS CoV2T immunoassay. The multiplex COVAM allows CCP to be grouped according to antibody reactivity patterns against 11 SARS-CoV-2 antigens. Unsupervised K-means analysis, via the gap statistics, as well as hierarchical clustering analysis revealed three main clusters with distinct reactivity intensities and patterns. These patterns were not recapitulated by adjusting the VITROS CoV2T or RVPNT assay thresholds. Plasma classified by COVAM reactivity patterns offers potential to improve CCP therapeutic efficacy CoV2T alone. The use of a SARS-CoV-2 antigen array can qualify CCP for administration as a treatment for acute COVID-19, and interrogate vaccine immunogenicity and performance in preclinical, clinical studies, and routine vaccination to identify antibody responses predictive of protection from infection and disease.

Abstract Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral infection caused by Crimean-Congo hemorrhagic fever virus (CCHFV). Serological screening of CCHF is important and current ELISA use antigens prepared from virus which is expensive due to requirement of high bio-containment facilities. In this study, we aimed to develop a new recombinant ELISA. For this purpose, CCHFV genome were expressed as 13 proteins in E. coli and among them abundantly purified recombinant Nucleocapsid protein (rNP) and Mucin-like variable domain (rMLD) were used as antigen in ELISA (Rec-ELISA). Rec-ELISA using rNP, rMLD and a combination of both (rNP/rMLD) were probed with acute (n = 64; collected between days 1 and 7 after onset of symptoms), convalescent (n = 35; collected 8 days after onset of symptoms), consecutive sera (n = 25) of confirmed CCHF cases and control sera (n = 43). The sensitivity and specificity of Rec-ELISA using rNP/rMLD were 73% and 98% in acute cases and 97% and 98% in convalescent cases. The median interquartile absorbance value to discriminate the acute and convalescent phases of CCHF was significantly higher with ELISA using rNP/rMLD (P 0.05) and rMLD (P = 0.001). These results indicate that the Rec-ELISA using rNP/rMLD may be very useful to diagnose convalescent CCHF cases especially in field studies.

In 2020, the COVID-19 pandemic created disruption in many of the institutions we regularly rely on, including universities. While disruption may often bring with it a myriad of possible pitfalls, it affords potential opportunities for change and development by reflecting on and modifying practices. In this article, a group of learning advisors and administrators from a self-access center at an international university in Japan reflect on the ruptures we experienced as a result of changes due to unexpectedly working remotely and our attempts to find stability, the pitfalls we sought to avoid, and the opportunities that we found amidst the disruption. Specifically, we illustrate our experiences related to student-led learning communities, self-access curricula, and learning advising, considering the effect on students and advisors alike. We advocate that self-access practitioners actively promote the use of language, encourage the development of communities of learners who focus on their interests, offer full online services even when the center is open, and use the same effective practices whether supporting learners online or offline. Our intention is that this article will help others to support stability, connectivity, and positive development in their own contexts.

Background: The limitations of ‘knowledge transfer’ are increasingly recognised, with growing interest in ‘knowledge co-production in context’. One way of achieving the latter is by ‘embedding’ researchers in health service settings, yet how to deliver such schemes successfully is poorly understood. Objectives: The objectives were to examine the nature of ‘embedded knowledge co-production’ and explore how embedded research initiatives can be designed more effectively. Design: The study used four linked workstreams. Workstream 1 involved two parallel literature reviews to examine how ‘knowledge co-production’ and ‘embedded research’ are conceptualised, operationalised and discussed. In workstream 2, a scoping review of exisiting or recent ‘embedded researcher’ schemes in UK health settings was carried out. Workstream 3 involved developing four in-depth case studies on such schemes to understand their mechanisms, effectiveness and challenges. In workstream 4, insights from the other workstreams were used to provide recommendations, guidance and templates for the different ways embedded co-production may be framed and specified. The overall goal was to help those interested in developing and using such approaches to understand and address the design choices they face. Setting: Embedded research initiatives in UK health settings. Data sources: Data were sourced from the following: analysis of the published and grey literature (87 source articles on knowledge co-production, and 47 published reports on extant embedded research initiatives), documentation and interviews with key actors across 45 established embedded research initiatives, in-depth interviews and site observations with 31 participants over 12 months in four intensive case studies, and informal and creative engagement in workshops (n = 2) and with participants in embedded research initiatives who joined various managed discussion forums. Participants: The participants were stakeholders and participants in embedded research initiatives. Results: The literature reviews from workstream 1 produced practical frameworks for understanding knowledge co-production and embedded research initiatives, which, with the scoping review (workstream 2), informed the identification and articulation of 10 design concerns under three overarching categories: intent (covering outcomes and power dynamics), structures (scale, involvement, proximity and belonging) and processes (the functional activities, skills and expertise required, nature of the relational roles, and the learning mechanisms employed). Current instances of embedded research were diverse across many of these domains. The four case studies (workstream 3) added insights into scheme dynamics and life cycles, deepening understanding of the overarching categories and showing the contingencies experienced in co-producing knowledge. A key finding is that there was often a greater emphasis on embeddedness per se than on co-production, which can be hard to discern. Finally, the engaging and influencing activities running throughout (workstream 4) allowed these research-rooted insights to be translated into practical tools and resources, evidenced by peer-reviewed publications, for those interested in exploring and developing the approach. Conclusions: Embedded research has a strong underpinning rationale, and more is becoming known about its design and management challenges. The tools and resources developed in this project provide a coherent evidence-informed framework for designing, operationalising and managing such schemes. It cannot yet be said with clarity that the potential benefits of embedded research are always deliverable, nor what the cost would be. Future work: With the means to describe and categorise different types of embedded research initiatives, more evaluative work is now needed to examine the relative merits and costs of different designs. Funding: This project was funded by the National Institute for Health Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 3. See the NIHR Journals Library website for further project information.

Abstract Background Naturally acquired immunity to malaria across the globe varies in intensity and protective powers. Many of the studies on immunity are from hyperendemic regions of Africa. In Asia, particularly in India, there are unique opportunities for exploring and understanding malaria immunity relative to host age, co-occurrence of Plasmodium falciparum and Plasmodium vivax infections, varying travel history, and varying disease severity. Variation in immunity in hospital settings is particularly understudied. Methods A US NIH ICEMR (South Asia) team examined the level of immunity in an Indian malaria patient population visiting or admitted to Goa Medical College and Hospital in Goa, India. Sera from 200 patients of different ages, in different seasons, infected with P. falciparum or P. vivax or both species, and with different clinical severity were applied to an established protein array system with over 1000 P. falciparum and P. vivax antigens. Differential binding of patient IgG to different antigens was measured. Results Even though Goa itself has much more P. vivax than P. falciparum, IgG reactivity towards P. falciparum antigens was very strong and comparable to that seen in regions of the world with high P. falciparum endemicity. Of 248 seropositive P. falciparum antigens, the strongest were VAR, MSP10, HSP70, PTP5, AP2, AMA1, and SYN6. In P. vivax patients, ETRAMPs, MSPs, and ApiAP2, sexual stage antigen s16, RON3 were the strongest IgG binders. Both P. falciparum and P. vivax patients also revealed strong binding to new antigens with unknown functions. Seropositives showed antigens unique to the young (HSP40, ACS6, GCVH) or to non-severe malaria (MSP3.8 and PHIST). Conclusion Seroreactivity at a major hospital in Southwest India reveals antibody responses to P. falciparum and P. vivax in a low malaria transmission region with much migration. In addition to markers of transmission, the data points to specific leads for possible protective immunity against severe disease. Several, but not all, key antigens overlap with work from different settings around the globe and from other parts of India. Together, these studies confidently help define antigens with the greatest potential chance of universal application for surveillance and possibly for disease protection, in many different parts of India and the world.

Welcome to the final issue of SiSAL journal for 2021. The cover picture for this issue was kindly provided by Elizabeth Lavolette and is a festive scene from Kyoto Sangyo University. Decorations and themed events in self-access centres in Japan are popular at this time of year, and on that note, we wish everyone a peaceful holiday and all the best for 2022. We would especially like to thank everyone who contributed articles to SiSAL Journal this year and to all the reviewers and editorial team members, especially the Associate Editor Robert Werner. As we go into the 13th year of the journal, we feel proud that with everyone’s help, we can publish four open-access issues of SiSAL Journal each year. We hope you enjoy the three articles and two reviews in this issue. We were inspired by the innovative research approaches, for example, visual narratives (Howard et al.; Kashiwa), in-depth interviews (Kashiwa; Lavolette & Claflin), and learning space analysis using typologies (Lavolette & Claflin). The authors also highlight the important roles of peers in the learning process (Panmei & Waluyo; Howard et al.; Kashiwa).

Globally and regionally, there is an increasing impetus to electrify the road transport system. The diversity and complexity of the road transport system pose several challenges to electrification in sectors that have higher energy usage requirements. Electric road systems (ERS) have the potential for a balancing solution. An ERS is not only an engineering project, but it is also an innovation system that is complex and composed of multiple stakeholders, requiring an interdisciplinary means of aligning problems, relations, and solutions. This study looked to determine the political, economic, social, and technical (PEST) factors by actively engaging UK stakeholders through online in-depth and semi-structured discussions. The focus is on dynamic wireless power transfer (DWPT) due to its wider market reach and on the basis that a comprehensive review of the literature indicated that the current focus is on the technical challenges and hence there is a gap in the knowledge around application requirements, which is necessary if society is to achieve its goals of electrification and GHG reduction. Qualitative analysis was undertaken to identify factors that are critical to the success of a DWPT system. The outcome of this study is knowledge of the factors that determine the function and market acceptance of DWPT. These factors can be grouped into six categories: vehicle, journey, infrastructure, economic, traffic and behaviour. These factors, the associated probability distributions attributable to these factors and the relations between them (logic functions), will form the basis for decision making when implementing DWPT as part of the wider UK electric vehicle charging infrastructure and hence support the ambition to electrify all road transport. The results will make a significant contribution to the emerging knowledge base on ERS and specifically DWPT.

Abstract Our understanding of the structure and regulation of Plasmodium vivax genes is limited by our inability to grow the parasites in long-term in vitro cultures. Most P. vivax studies must therefore rely on patient samples, which typically display a low proportion of parasites and asynchronous parasites. Here, we present stranded RNA-seq data generated directly from a small volume of blood from three Cambodian vivax malaria patients collected before treatment. Our analyses show surprising similarities of the parasite gene expression patterns across infections, despite extensive variations in parasite stage proportion. These similarities contrast with the unique gene expression patterns observed in sporozoites isolated from salivary glands of infected Colombian mosquitoes. Our analyses also indicate that more than 10% of P. vivax genes encode multiple, often undescribed, protein-coding sequences, potentially increasing the diversity of proteins synthesized by blood stage parasites. These data also greatly improve the annotations of P. vivax gene untranslated regions, providing an important resource for future studies of specific genes.

Charter Party agreements underpin the relationship between ship owners and charterers. The agreement guarantees the performance of a vessel in terms of speed and fuel consumption. On this basis the charterers plan the arrival of their cargo and their profit margin. However, ship performance is degraded by age, periods between maintenance and many vessels fail to perform as expected. Moreover the performance is only warranted during the specific conditions stated in the charter party which are not always clear. These usually refer to Beaufort Force (BF) and the Douglas Sea and Swell (DSS) scale which is archaic in the age of Numerical Weather Prediction. Given these conditions, the stage is set for conflict and there are often disputes over the weather conditions experienced. Moreover ships’ often do not arrive on time because the charterer has assumed that the ship will make good its warranted speed and not taken account of the forecast weather conditions. The authors propose a new way of approaching charter agreements with the emphasis on consultation rather than confrontation facilitated by a new web based software platform.

Abstract Background Severe limb ischaemia (SLI) is defined as the presence of rest pain and/or tissue loss secondary to lower extremity atherosclerotic peripheral arterial disease. The superficial femoral and popliteal arteries are the most commonly diseased vessels in such patients and are being increasingly treated using endovascular revascularisation techniques. However, it is currently unknown whether drug-eluting stents and drug-coated balloons confer additional clinical benefits over more established techniques using plain balloons and bare metal stents, or whether they represent a cost-effective use of NHS resources. Methods The BASIL-3 trial is a UK National Institute for Health Research, Health Technology Assessment Programme-funded, multicentre, randomised controlled trial (RCT) comparing the clinical and cost-effectiveness of plain balloon angioplasty with or without bail-out bare metal stenting, drug-coated balloon angioplasty with or without bail-out bare metal stenting, and primary stenting with drug-eluting stents for SLI secondary to femoro-popliteal disease. Patients with ‘multilevel’ disease may receive aorto-iliac and/or infrapopliteal treatments concurrently with their randomised femoro-popliteal intervention. The primary clinical outcome is amputation-free survival defined as the time to major (above the ankle) amputation of the index limb or death from any cause. The primary outcome for the economic analysis is cost per quality-adjusted life year. Secondary outcome measures include overall survival, major adverse limb events, major adverse cardiac events, relief of ischaemic pain, healing of tissue loss, and quality of life. The required sample size has been calculated at 861 participants (287 on each arm). These patients will be recruited over 3 years and followed-up for between 2 and 5 years. Discussion BASIL-3 is a pragmatic RCT designed to reflect current UK clinical practice. The results will inform decision-making regarding the appropriateness of funding the use of drug-coated balloons and drug-eluting stents, by the NHS, for the management of SLI due to femoro-popliteal disease. Trial registration ISRCTN Registry, identifier: ISRCTN14469736 . Registered on 22 October 2015.

In the Self-Access Learning Center (SALC) at a university in Japan, language learners create and implement individual learning plans. Strategies to facilitate reflective dialogue are used by learning advisors to encourage these learners to pursue their language goals and become increasingly less reliant on direction from their teachers. In this paper, a definition for autonomy is given, and the teaching setting is introduced, giving an overview of the SALC and outlining the ways learners use it, drawing on examples of learners at different stages on their journey to autonomy. After looking at theory and practical applications, this paper demonstrates that guiding learners through dialogue is an appropriate way to challenge meanings and raise consciousness, and move learners towards managing their own language learning.

In the real world, the severity of traumatic injuries is measured using the Abbreviated Injury Scale (AIS). However, the AIS scale cannot currently be computed by using the output from finite element human computer models, which currently rely on maximum principal strains (MPS) to capture serious and fatal injuries. In order to overcome these limitations, a unique Organ Trauma Model (OTM) able to calculate the threat to the life of a brain model at all AIS levels is introduced. The OTM uses a power method, named Peak Virtual Power (PVP), and defines brain white and grey matter trauma responses as a function of impact location and impact speed. This research has considered ageing in the injury severity computation by including soft tissue material degradation, as well as brain volume changes due to ageing. Further, to account for the limitations of the Lagrangian formulation of the brain model in representing hemorrhage, an approach to include the effects of subdural hematoma is proposed and included as part of the predictions. The OTM model was tested against two real-life falls and has proven to correctly predict the post-mortem outcomes. This paper is a proof of concept, and pending more testing, could support forensic studies.

Background: There is compelling evidence to suggest that some (or even many) NHS staff feel unable to speak up, and that even when they do, their organisation may respond inappropriately. Objectives: The specific project objectives were (1) to explore the academic and grey literature on whistleblowing and related concepts, identifying the key theoretical frameworks that can inform an understanding of whistleblowing; (2) to synthesise the empirical evidence about the processes that facilitate or impede employees raising concerns; (3) to examine the legal framework(s) underpinning whistleblowing; (4) to distil the lessons for whistleblowing policies from the findings of Inquiries into failings of NHS care; (5) to ascertain the views of stakeholders about the development of whistleblowing policies; and (6) to develop practical guidance for future policy-making in this area. Methods: The study comprised four distinct but interlocking strands: (1) a series of narrative literature reviews, (2) an analysis of the legal issues related to whistleblowing, (3) a review of formal Inquiries related to previous failings of NHS care and (4) interviews with key informants. Results: Policy prescriptions often conceive the issue of raising concerns as a simple choice between deciding to ‘blow the whistle’ and remaining silent. Yet research suggests that health-care professionals may raise concerns internally within the organisation in more informal ways before utilising whistleblowing processes. Potential areas for development here include the oversight of whistleblowing from an independent agency; early-stage protection for whistleblowers; an examination of the role of incentives in encouraging whistleblowing; and improvements to criminal law to protect whistleblowers. Perhaps surprisingly, there is little discussion of, or recommendations concerning, whistleblowing across the previous NHS Inquiry reports. Limitations: Although every effort was made to capture all relevant papers and documents in the various reviews using comprehensive search strategies, some may have been missed as indexing in this area is challenging. We interviewed only a small number of people in the key informant interviews, and our findings may have been different if we had included a larger sample or informants with different roles and responsibilities. Conclusions: Current policy prescriptions that seek to develop better whistleblowing policies and nurture open reporting cultures are in need of more evidence. Although we set out a wide range of issues, it is beyond our remit to convert these concerns into specific recommendations: that is a process that needs to be led from elsewhere, and in partnership with the service. There is also still much to learn regarding this important area of health policy, and we have highlighted a number of important gaps in knowledge that are in need of more sustained research. Future work: A key area for future research is to explore whistleblowing as an unfolding, situated and interactional process and not just a one-off act by an identifiable whistleblower. In particular, we need more evidence and insights into the tendency for senior managers not to hear, accept or act on concerns about care raised by employees. Funding: The National Institute for Health Research Health Services and Delivery Research programme.

For every learning advisor and language teacher, a fundamental goal is to foster learners’ motivation and self-regulation for successful L2 learning. This paper presents a visual tool that can be used in advising and teaching to realize this purpose. With the tool, learners can review their own L2 learning and ability, and create an inventory of their learning strategies, which helps them find their weaknesses, goals and develop their approach. The tool, the Strategy Tree for Language Learners, consists of the image of a tree, water and the sun. The trunk and leaves of the tree represent learners’ linguistic knowledge and skills, the roots learners’ affective strategies, water cognitive strategies, and the sun sociocultural-interactive strategies. The notions of these three types of strategies are based on the concepts presented by Oxford (2011).

Road transport is recognized as having a negative impact on the environment. Policy has focused on replacement of the internal combustion engine (ICE) with less polluting forms of technology, including battery electric and fuel cell electric powertrains. However, progress is slow and both battery and fuel cell based vehicles face considerable commercialization challenges. To understand these challenges, a review of current electric battery and fuel cell electric technologies is presented. Based on this review, this paper proposes a battery electric vehicle (BEV) where components are sized to take into account the majority of user requirements, with the remainder catered for by a trailer-based demountable intelligent fuel cell range extender. The proposed design can extend the range by more than 50% for small BEVs and 25% for large BEVs (the extended range of vehicles over 250 miles), reducing cost and increasing efficiency for the BEV. It enables BEV manufacturers to design their vehicle battery for the most common journeys, decreases charging time to provide convenience and flexibility to the drivers. Adopting a rent and drop business model reduces the demand on the raw materials, bridging the gap in the amount of charging (refueling) stations, and extending the lifespan for the battery pack.

Background: Recent high-profile reports into serious failings in the quality of hospital care in the NHS raise concerns over the ability of trust boards to discharge their duties effectively. Objectives: Our study aimed to generate theoretically grounded empirical evidence on the associations between board governance, patient safety processes and patient-centred outcomes. The specific aims were as follows: (1) to identify the types of governance activities undertaken by hospital trust boards in the English NHS with regard to ensuring safe care in their organisation; (2) in foundation trusts, to explore the role of boards and boards of governors with regards to the oversight of patient safety in their organisation; (3) to assess the association between particular hospital trust board oversight activities and patient safety processes and clinical outcomes; (4) to identify the facilitators and barriers to developing effective hospital trust board governance of safe care; and (5) to assess the impact of external commissioning arrangements and incentives on hospital trust board oversight of patient safety. Methods: The study comprised three distinct but interlocking strands: (1) a narrative systematic review in order to describe, interpret and synthesise key findings and debates concerning board oversight of patient safety; (2) in-depth mixed-methods case studies in four organisations to assess the impact of hospital board governance and external incentives on patient safety processes and outcomes; and (3) two national surveys exploring board management in NHS acute and specialist hospital trusts in England, and relating board characteristics to whole-organisation outcomes. Results: A very high proportion of trust boards reported the kinds of desirable characteristics and board-related processes that research says may be associated with higher performance. Our analysis of the symbolic aspects of board activities highlights the role and differences in local processes of organising the governance of patient safety. Most boards do allocate a considerable amount of time to discussing patient safety and quality-related issues and were using a wide range of hard performance metrics and soft intelligence to monitor its organisation with regard to patient safety. Although the board of governors is generally perceived to be well-meaning, they were also considered to be being largely ineffective in helping to promote and deliver safer care for their organisations. We did not find any statistically significant relationship between board attributes (self-reported) and processes and any patient safety outcome measures. However, we did find a significant relationship between two dimensions of the Board Self-Assessment Questionnaire and two specific-and-related national staff survey organisational ‘process’ measures: (1) staff feeling safe to raise concerns about errors, near-misses and incidents and (2) staff feeling confident that their organisation would address their concerns, if raised. We also found that contracting and external financial incentives appeared to play only a relatively minor role in incentivising quality and safety improvement. Conclusions: Our research is the first large-scale mixed-methods study of hospital board activity and behaviour related to the oversight of patient safety in the English NHS and the key findings should be used to influence the design of future governance arrangements as well as the training and support of board. Our finding that board governance/competencies appear to be linked to staff feeling safe to raise concerns about patient safety issues, and also their confidence that their organisation would address their concern, is worthy of further and more sustained exploration, particularly in the context of the current focus on improving whistleblowing policies in the NHS. Funding: The National Institute for Health Research Health Services and Delivery Research programme.

There is an urgent need to produce a vaccine for Chlamydia trachomatis infections. Here, using the Chlamydia muridarum major outer membrane protein (MOMP) as an antigen, four adjuvant combinations IVAX-1 (MPLA+CpG-1018+AddaVax), IVAX-2 (MPLA+CpG-1018+AS03), CpG-1826+Montanide ISA 720 VG (CpG-1826+Mont) and CpG-1018+Montanide ISA 720 VG (CpG-1018+Mont), were tested for their local reactogenicity and ability to elicit protection in BALB/c mice against a respiratory challenge with C. muridarum. Immunization with IVAX-1 or IVAX-2 induced no significant local reactogenicity following intramuscular immunization. In contrast, vaccines containing Montanide resulted in the formation of a local granuloma. Based on the IgG2a/IgG1 ratio in serum, the four adjuvant combinations elicited Th1-biased responses. IVAX-1 induced the highest in vitro neutralization titers while CpG-1018+Mont stimulated the lowest. As determined by the levels of IFN-γ produced by T-cells, the most robust cellular immune responses were elicited in mice immunized with CpG-1018+Mont, while the weakest responses were mounted by mice receiving IVAX-1. Following the respiratory challenge, mice immunized with CpG-1018+Mont lost the least amount of body weight and had the lowest number of C. muridarum inclusion-forming units (IFUs) in the lungs, while those receiving IVAX-2 had lost the most weight and had the highest number of IFUs in their lungs. Animals vaccinated with CpG-1826+Mont had the lightest lungs while those immunized using IVAX-2 had the heaviest. To conclude, due to their safety and adjuvanticity, IVAX formulations should be considered for inclusion in human vaccines against Chlamydia.

High-throughput and rapid screening testing is highly desirable to effectively combat the rapidly evolving COVID-19 pandemic co-presents with influenza and seasonal common cold epidemics. Here, we present a general workflow for iterative development and validation of an antibody-based microarray assay for the detection of a respiratory viral panel: (a) antibody screening to quickly identify optimal reagents and assay conditions, (b) immunofluorescence assay design including signal amplification for low viral titers, (c) assay characterization with recombinant proteins, inactivated viral samples and clinical samples, and (d) multiplexing to detect a panel of common respiratory viruses. Using RT-PCR-confirmed SARS-CoV-2 positive and negative pharyngeal swab samples, we demonstrated that the antibody microarray assay exhibited a clinical sensitivity and specificity of 77.2% and 100%, respectively, which are comparable to existing FDA-authorized antigen tests. Moreover, the microarray assay is correlated with RT-PCR cycle threshold (Ct) values and is particularly effective in identifying high viral titers. The multiplexed assay can selectively detect SARS-CoV-2 and influenza virus, which can be used to discriminate these viral infections that share similar symptoms. Such protein microarray technology is amenable for scale-up and automation and can be broadly applied as a both diagnostic and research tool.

Current seasonal and pre-pandemic influenza vaccines induce short-lived predominantly strain-specific and limited heterosubtypic responses. To better understand how vaccine adjuvants AS03 and MF59 may provide improved antibody responses to vaccination, we interrogated serum from subjects who received 2 doses of inactivated monovalent influenza A/Indonesia/05/2005 vaccine with or without AS03 or MF59 using hemagglutinin (HA) microarrays (NCT01317758 and NCT01317745). The arrays were designed to reflect both full-length and globular head HA derived from 17 influenza A subtypes (H1 to H16 and H18) and influenza B strains. We observed significantly increased strain-specific and broad homo- and heterosubtypic antibody responses with both AS03 and MF59 adjuvanted vaccination with AS03 achieving a higher titer and breadth of IgG responses relative to MF59. The adjuvanted vaccine was also associated with the elicitation of stalk-directed antibody. We established good correlation of the array antibody responses to H5 antigens with standard HA inhibition and microneutralization titers.

BackgroundDespite largely successful control efforts, malaria remains a significant public health problem in Thailand. Based on microscopy, the northwestern province of Tak, once Thailand's highest burden area, is now considered a low-transmission region. However, microscopy is insensitive to detect low-level parasitaemia, causing gross underestimation of parasite prevalence in areas where most infections are subpatent. The objective of this study was to assess the current epidemiology of malaria prevalence using molecular and serological detection methods, and to profile the antibody responses against Plasmodium as it relates to age, seasonal changes and clinical manifestations during infection. Three comprehensive cross-sectional surveys were performed in a sentinel village and from febrile hospital patients, and whole blood samples were collected from infants to elderly adults. Genomic DNA isolated from cellular fraction was screened by quantitative-PCR for the presence of Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale and Plasmodium knowlesi. Plasma samples were probed on protein microarray to obtain antibody response profiles from the same individuals.ResultsWithin the studied community, 90.2 % of Plasmodium infections were submicroscopic and asymptomatic, including a large number of mixed-species infections. Amongst febrile patients, mixed-species infections comprised 68 % of positive cases, all of which went misdiagnosed and undertreated. All samples tested showed serological reactivity to Plasmodium antigens. There were significant differences in the rates of antibody acquisition against P. falciparum and P. vivax, and age-related differences in species-specific immunodominance of response. Antibodies against Plasmodium increased along the ten-month study period. Febrile patients had stronger antibody responses than asymptomatic carriers.ConclusionsDespite a great decline in malaria prevalence, transmission is still ongoing at levels undetectable by traditional methods. As current surveillance methods focus on case management, malaria transmission in Thailand will not be interrupted if asymptomatic submicroscopic infections are not detected and treated.