Relevance of microRNAs in SARS-CoV-2 infection of primary human hepatocytes

Introduction Entry factors angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) facilitate Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) entry into the host cells. Despite SARS-CoV-2s preference for respiratory system, extra-pulmonary organ involvement has been suggested. Recent studies report that SARS-CoV-2 leads to direct hepatic impairment in COVID-19 patients, necessitating further investigations about hepatic involvement. ACE2 and TMPRSS2 are expressed in primary human hepatocytes (PHH), suggesting a possible susceptibility to SARS-CoV-2. Despite this, data on infection and factors modulating functional regulation of SARS-CoV-2 infection in PHH are lacking. MicroRNAs (miRNAs) are approximately 22 nucleotide-long non-coding RNAs that have been shown to regulate various cellular processes including virus-host interactions. We aimed to study the susceptibility of PHH to SARS-CoV-2 and to evaluate the potential of miRNAs in modulating viral infection. Materials and methods We investigated the role of miRNAs to regulate SARS-CoV-2 infection in PHH in vitro. To strengthen our fndings, we analysed liver autopsies from COVID-19 patients. Results We demonstrate that PHH can be readily infected with SARS-CoV-2, resulting in robust replication and sustained host responses as indicated by the upregulation of several interferon-stimulated genes. In silico analyses unravelled miR-200c-3p, miR-429 and miR-141-3p as candidate miRNAs targeting ACE2 and, let-7c-5p targeting TMPRSS2. Expression of these miRNAs reduced SARS-CoV-2 infection in PHH. Furthermore, expression of several endogenous miRNAs was altered upon SARS-CoV-2 infection in PHH and human liver autopsies. Conclusion Our results show that PHH are susceptible towards SARS-CoV-2 and cellular miRNAs can diminish SARS-CoV-2 viral burden.

COVID-19: the relationship between perceptions of risk and behaviours during lockdown.

AIM: Understanding COVID-19 risk perceptions and their impact on behaviour can improve the effectiveness of public health strategies. Prior evidence suggests that, when people perceive uncontrollable risks to their health, they are less likely to engage in healthful behaviour. This article aims to understand the extent to which COVID-19 is perceived as an uncontrollable risk, and to assess whether this perceived risk is associated with health behaviour. SUBJECT AND METHODS: We surveyed a nationally representative sample of 496 participants during the first UK lockdown. We assessed perceptions of COVID-19-related risk, self-reported adherence to infection control measures recommended by the UK Government, and general health behaviours. We predicted that increased perceived extrinsic mortality risk (the portion of mortality risk perceived to be uncontrollable) would disincentivise healthy behaviour. RESULTS: Perceived threat to life was the most consistent predictor of reported adherence to infection control measures. Perceived extrinsic mortality risk was found to have increased due to the pandemic, and was associated with lower reported adherence to Government advice on diet, physical activity, and smoking. CONCLUSIONS: Our findings suggest that health messages that highlight threat to life may be effective in increasing adherence to infection control, but may also lead to a reduction in health-promoting behaviours. We suggest that messages that highlight threat to life should be accompanied by statements of efficacy. Further, messages evoking feelings of concern for others may be effective in promoting compliance with anti-infection measures, without the potential for the unwelcome side-effect of discouraging healthy behaviour. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10389-021-01543-9.

Mothers' accounts of the impact of being in nature on postnatal wellbeing: a focus group study.

BACKGROUND: The postnatal period is a vulnerable time for mothers to experience stress and mental health difficulties. There is increasing evidence that spending time in nature is beneficial for wellbeing. Nature-based interventions have been developed to support mental health, but not specifically tailored for mothers during the postnatal period. Understanding mothers' views and experiences of nature would help determine the suitability for and potential impact of such interventions on postnatal wellbeing. AIMS: To explore mothers' views on the impact of spending time in nature on their postnatal mental wellbeing. METHODS: Focus groups were held with mothers of young children (under five), including mothers from migrant and refugee communities, mothers living with mental health difficulties, and disabled mothers. Data were analysed using reflexive thematic analysis. RESULTS: Four focus groups were held, with a total of 30 participants. Six themes were developed: (1) mothers' experiences of what constitutes 'nature'; (2) sensing nature improves wellbeing; (3) natural spaces facilitate human connection; (4) nature provides escape and relief from daily indoor stressors; (5) nature allows new perspectives; and (6) mothers face a variety of environmental, practical, psychological, physical, socioeconomic, and cultural barriers to spending time in nature during the postnatal period. CONCLUSIONS: Mothers report significant benefits to their postnatal wellbeing when spending time in nature. Further research is warranted to understand whether nature-based interventions have the potential to support postnatal wellbeing, socially, mentally, and physically.

The effect of a change from face-to-face to remote positive airway pressure education for patients with sleep apnoea during the coronavirus disease-2019 pandemic: a prospective cohort study.

Background: The coronavirus disease-2019 (COVID-19) pandemic and national lockdowns necessitated a change in service delivery including positive airway pressure (PAP) education protocols, with no data on how this may impact subsequent PAP adherence. We aim to quantify adherence of PAP initiated during the COVID-19 pandemic and compare the effects of remote versus face-to-face (FTF) education in patients with obstructive sleep apnoea (OSA). Methods: This prospective cohort study in a tertiary National Health Service (NHS) hospital sleep disorders centre in London, United Kingdom, included 141 patients aged >18 years with newly diagnosed OSA initiating PAP during the COVID-19 pandemic; 71 patients receiving standard FTF education compared to 70 patients educated on PAP remotely at the start of lockdown. Results: Adherence over a consecutive 30-day period within the first three months of PAP usage was measured, secondary outcomes included average nightly usage, usage per nights used, percentage of nights used, and percentage of nights used for ≥4 hours. In 141 patients (two-thirds male, 56% of at least 45 years of age and 48.9% sleepy at baseline), 114 patients (81%) were diagnosed with moderate or severe OSA. 54 patients (38.3%) achieved good adherence (≥70% of nights with ≥4 hours usage), with an average of 4.7 hours of PAP usage per night used. Patients receiving FTF PAP education had a comparable level of good adherence (38% versus 38.6%, P=0.915), and hours per nights used (4.7 versus 4.6 h/night, P=0.711) to remotely educated patients. More severe OSA, lower mask leak, and a nasal mask were associated with achieving good PAP adherence. Conclusions: PAP adherence of newly diagnosed individuals with OSA during the COVID-19 pandemic was modest at 38.30%, and not significantly affected by remote PAP education delivery.

Learning from pandemic responses: Informing a resilient and equitable health system recovery in Thailand.

This article is part of the Research Topic 'Health Systems Recovery in the Context of COVID-19 and Protracted Conflict'. The third quarter of 2022 saw COVID-19 cases and deaths in Thailand reduced significantly, and high levels of COVID-19 vaccine coverage. COVID-19 was declared an "endemic" disease, and economic activities resumed. This paper reviews pre-pandemic health systems capacity and identifies pandemic response strengths, weaknesses and lessons that guided resilient and equitable health system recovery. Robust health systems and adaptive strategies drive an effective pandemic response. To support health system recovery Thailand should (1) minimize vulnerability and extend universal health coverage to include migrant workers and dependents; (2) sustain provincial primary healthcare (PHC) capacity and strengthen PHC in greater Bangkok; (3) leverage information technology for telemedicine and teleconsultation; (4) enhance and extend case and event-based surveillance of notifiable diseases, and for public health threats, including pathogens with pandemic potential in wildlife and domesticated animals. This requires policy and financial commitment across successive governments, adequate numbers of committed and competent health workforce at all levels supported by over a million village health volunteers, strong social capital and community resilience. A strengthened global health architecture and international collaboration also have critical roles in establishing local capacities to develop and manufacture pandemic response products through transfer of technology and know-how. Countries should engage in the ongoing Inter-government Negotiating Body to ensure a legally binding instrument to safeguard the world from catastrophic impacts of future pandemics.

Learning from pandemic responses: Informing a resilient and equitable health system recovery in Thailand

This article is part of the Research Topic ‘Health Systems Recovery in the Context of COVID-19 and Protracted Conflict'. The third quarter of 2022 saw COVID-19 cases and deaths in Thailand reduced significantly, and high levels of COVID-19 vaccine coverage. COVID-19 was declared an "endemic” disease, and economic activities resumed. This paper reviews pre-pandemic health systems capacity and identifies pandemic response strengths, weaknesses and lessons that guided resilient and equitable health system recovery. Robust health systems and adaptive strategies drive an effective pandemic response. To support health system recovery Thailand should (1) minimize vulnerability and extend universal health coverage to include migrant workers and dependents;(2) sustain provincial primary healthcare (PHC) capacity and strengthen PHC in greater Bangkok;(3) leverage information technology for telemedicine and teleconsultation;(4) enhance and extend case and event-based surveillance of notifiable diseases, and for public health threats, including pathogens with pandemic potential in wildlife and domesticated animals. This requires policy and financial commitment across successive governments, adequate numbers of committed and competent health workforce at all levels supported by over a million village health volunteers, strong social capital and community resilience. A strengthened global health architecture and international collaboration also have critical roles in establishing local capacities to develop and manufacture pandemic response products through transfer of technology and know-how. Countries should engage in the ongoing Inter-government Negotiating Body to ensure a legally binding instrument to safeguard the world from catastrophic impacts of future pandemics.

Vaccine-associated enhanced respiratory pathology in COVID-19 hamsters after TH2-biased immunization.

Vaccine-associated enhanced respiratory disease (VAERD) is a severe complication for some respiratory infections. To investigate the potential for VAERD induction in coronavirus disease 2019 (COVID-19), we evaluate two vaccine leads utilizing a severe hamster infection model: a T helper type 1 (TH1)-biased measles vaccine-derived candidate and a TH2-biased alum-adjuvanted, non-stabilized spike protein. The measles virus (MeV)-derived vaccine protects the animals, but the protein lead induces VAERD, which can be alleviated by dexamethasone treatment. Bulk transcriptomic analysis reveals that our protein vaccine prepares enhanced host gene dysregulation in the lung, exclusively up-regulating mRNAs encoding the eosinophil attractant CCL-11, TH2-driving interleukin (IL)-19, or TH2 cytokines IL-4, IL-5, and IL-13. Single-cell RNA sequencing (scRNA-seq) identifies lung macrophages or lymphoid cells as sources, respectively. Our findings imply that VAERD is caused by the concerted action of hyperstimulated macrophages and TH2 cytokine-secreting lymphoid cells and potentially links VAERD to antibody-dependent enhancement (ADE). In summary, we identify the cytokine drivers and cellular contributors that mediate VAERD after TH2-biased vaccination.

The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses.

The lipid envelope of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an essential component of the virus; however, its molecular composition is undetermined. Addressing this knowledge gap could support the design of antiviral agents as well as further our understanding of viral-host protein interactions, infectivity, pathogenicity, and innate immune system clearance. Lipidomics revealed that the virus envelope comprised mainly phospholipids (PLs), with some cholesterol and sphingolipids, and with cholesterol/phospholipid ratio similar to lysosomes. Unlike cellular membranes, procoagulant amino-PLs were present on the external side of the viral envelope at levels exceeding those on activated platelets. Accordingly, virions directly promoted blood coagulation. To investigate whether these differences could enable selective targeting of the viral envelope in vivo, we tested whether oral rinses containing lipid-disrupting chemicals could reduce infectivity. Products containing PL-disrupting surfactants (such as cetylpyridinium chloride) met European virucidal standards in vitro; however, components that altered the critical micelle concentration reduced efficacy, and products containing essential oils, povidone-iodine, or chlorhexidine were ineffective. This result was recapitulated in vivo, where a 30-s oral rinse with cetylpyridinium chloride mouthwash eliminated live virus in the oral cavity of patients with coronavirus disease 19 for at least 1 h, whereas povidone-iodine and saline mouthwashes were ineffective. We conclude that the SARS-CoV-2 lipid envelope i) is distinct from the host plasma membrane, which may enable design of selective antiviral approaches; ii) contains exposed phosphatidylethanolamine and phosphatidylserine, which may influence thrombosis, pathogenicity, and inflammation; and iii) can be selectively targeted in vivo by specific oral rinses.

COVID-19-related changes in outpatient CPAP setup pathways for OSA are linked with decreased 30-day CPAP usage.

The COVID-19 pandemic changed continuous positive airway pressure (CPAP) setup pathways. We evaluated patients commenced on CPAP in 2019 (prepandemic) and 2020 (post-first UK wave). Face-to-face (F2F) setup numbers, with CPAP turned on, decreased from 613 patients (98.9%) in 2019, to 6 (1.1%) in 2020. In 2020, setups were F2F without CPAP turned on (403 (71.1%)), or remote (158 (27.9%)). Prepandemic median CPAP usage at first follow-up was 5.4 (2.7-6.9) hours/night and fell by 0.9 hours/night (95% CI 0.5 to 1.2, p<0.0001) in 2020. We found clinically relevant reductions in CPAP usage with pathway changes post-COVID-19.

Understanding the Barriers and Facilitators to Sharing Patient-Generated Health Data Using Digital Technology for People Living With Long-Term Health Conditions: A Narrative Review.

Using digital technology to share patient-generated health data has the potential to improve the self-management of multiple long-term health conditions. Sharing these data can allow patients to receive additional support from healthcare professionals and peer communities, as well as enhance their understanding of their own health. A deeper understanding of the concerns raised by those living with long-term health conditions when considering whether to share health data via digital technology may help to facilitate effective data sharing practices in the future. The aim of this review is to identify whether trust, identity, privacy and security concerns present barriers to the successful sharing of patient-generated data using digital technology by those living with long-term health conditions. We also address the impact of stigma on concerns surrounding sharing health data with others. Searches of CINAHL, PsychInfo and Web of Knowledge were conducted in December 2019 and again in October 2020 producing 2,581 results. An iterative review process resulted in a final dataset of 23 peer-reviewed articles. A thorough analysis of the selected articles found that issues surrounding trust, identity, privacy and security clearly present barriers to the sharing of patient-generated data across multiple sharing contexts. The presence of enacted stigma also acts as a barrier to sharing across multiple settings. We found that the majority of literature focuses on clinical settings with relatively little attention being given to sharing with third parties. Finally, we suggest the need for more solution-based research to overcome the discussed barriers to sharing.

The Human Liver-Expressed Lectin CD302 Restricts Hepatitis C Virus Infection.

C-type lectin domain-containing proteins (CTLDcps) shape host responses to pathogens and infectious disease outcomes. Previously, we identified the murine CTLDcp Cd302 as restriction factor, limiting hepatitis C virus (HCV) infection of murine hepatocytes. In this study, we investigated in detail the human orthologue's ability to restrict HCV infection in human liver cells. CD302 overexpression in Huh-7.5 cells potently inhibited infection of diverse HCV chimeras representing seven genotypes. Transcriptional profiling revealed abundant CD302 mRNA expression in human hepatocytes, the natural cellular target of HCV. Knockdown of endogenously expressed CD302 modestly enhanced HCV infection of Huh-7.5 cells and primary human hepatocytes. Functional analysis of naturally occurring CD302 transcript variants and engineered CD302 mutants showed that the C-type lectin-like domain (CTLD) is essential for HCV restriction, whereas the cytoplasmic domain (CPD) is dispensable. Coding single nucleotide polymorphisms occurring in human populations and mapping to different domains of CD302 did not influence the capacity of CD302 to restrict HCV. Assessment of the anti-HCV phenotype at different life cycle stages indicated that CD302 preferentially targets the viral entry step. In contrast to the murine orthologue, overexpression of human CD302 did not modulate downstream expression of nuclear receptor-controlled genes. Ectopic CD302 expression restricted infection of liver tropic hepatitis E virus (HEV), while it did not affect infection rates of two respiratory viruses, including respiratory syncytial virus (RSV) and the alpha coronavirus HVCoV-229E. Together, these findings suggest that CD302 contributes to liver cell-intrinsic defense against HCV and might mediate broader antiviral defenses against additional hepatotropic viruses. IMPORTANCE The liver represents an immunoprivileged organ characterized by enhanced resistance to immune responses. However, the importance of liver cell-endogenous, noncytolytic innate immune responses in pathogen control is not well defined. Although the role of myeloid cell-expressed CTLDcps in host responses to viruses has been characterized in detail, we have little information about their potential functions in the liver and their relevance for immune responses in this organ. Human hepatocytes endogenously express the CTLDcp CD302. Here, we provide evidence that CD302 limits HCV infection of human liver cells, likely by inhibiting a viral cell entry step. We confirm that the dominant liver-expressed transcript variant, as well as naturally occurring coding variants of CD302, maintain the capacity to restrict HCV. We further show that the CTLD of the protein is critical for the anti-HCV activity and that overexpressed CD302 limits HEV infection. Thus, CD302 likely contributes to human liver-intrinsic antiviral defenses.

Adsorption of environmental contaminants on micro- and nano-scale plastic polymers and the influence of weathering processes on their adsorptive attributes.

Increases in plastic-related pollution and their weathering can be a serious threat to environmental sustainability and human health, especially during the present COVID-19 (SARS-CoV-2 coronavirus) pandemic. Planetary risks of plastic waste disposed from diverse sources are exacerbated by the weathering-driven alterations in their physical-chemical attributes and presence of hazardous pollutants mediated through adsorption. Besides, plastic polymers act as vectors of toxic chemical contaminants and pathogenic microbes through sorption onto the 'plastisphere' (i.e., plastic-microbe/biofilm-environment interface). In this review, the effects of weathering-driven alterations on the plastisphere are addressed in relation to the fate/cycling of environmental contaminants along with the sorption/desorption dynamics of micro-/nano-scale plastic (MPs/NPs) polymers for emerging contaminants (e.g., endocrine-disrupting chemicals (EDCs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), pharmaceuticals and personal care products (PPCPs), and certain heavy metals). The weathering processes, pathways, and mechanisms governing the adsorption of specific environmental pollutants on MPs/NPs surface are thus evaluated in relation to the physicochemical alterations based on several kinetic and isotherm studies. Consequently, the detailed evaluation on the role of the complex associations between weathering and physicochemical properties of plastics should help us gain a better knowledge with respect to the transport, behavior, fate, and toxicological chemistry of plastics along with the proper tactics for their sustainable remediation.

Positive airway pressure adherence and remote versus face-to-face education for sleep apnoea during the novel coronavirus (COVID-19) pandemic

IntroductionWe aim to quantify adherence of positive airway pressure (PAP) initiated during the COVID-19 pandemic and compare the effects of remote versus face-to-face (FTF) education in patients with obstructive sleep apnoea (OSA).MethodsProspective cohort study in a tertiary National Health Service (NHS) hospital sleep disorders centre in London, United Kingdom, involving 141 patients aged >18 years with newly diagnosed OSA initiating PAP during the first national coronavirus (COVID-19) lockdown in 2020. We compare 70 patients educated on PAP remotely to 71 patients receiving standard FTF education. We measured adherence over a continuous 30-day period within the first three months of PAP usage, including average nightly usage, usage per nights used, percentage of nights used, and percentage of nights used for >4 hours.ResultsOf 141 patients, there was a two-thirds male predominance, and half of the patients (56%) above 45 years of age and sleepy at baseline (Epworth Sleepiness Score >10, 48.9%). 114 patients (81%) were diagnosed with moderate or severe OSA. 54 patients (38.3%) achieved good adherence (≥70% of nights with ≥4 hours usage), with an average of 4.7 hours of PAP usage per night used. Patients receiving FTF PAP education had a comparable level of good adherence (38.03% versus 38.57%, p=0.915), and hours per nights used (4.76 versus 4.61 h/night, p=0.711) to remotely educated patients. More severe OSA, lower mask leak, and a nasal mask were associated with achieving good PAP adherence.DiscussionPAP adherence of newly diagnosed individuals with OSA during the COVID-19 pandemic was modest at 38.30%, and not significantly affected by remote PAP education delivery, but rather the effects of the COVID-19 pandemic.

Enhancing junior doctor leadership and management skills as innovation fellows

AimsThe Site Innovation Lead at Wrexham Maelor Hospital, Betsi Cadwaladr University Health Board appointed 12 junior doctors as Innovation Fellows in order to enhance their leadership and management skills.MethodsJunior doctors competitively applied to be a Wrexham Innovation Fellow. This formal leadership position included mentoring from the Site Innovation Lead and quality improvement (QI) training. Each Innovation Fellow was guided and encouraged to undertake the Improving Quality Together’ (IQT) Welsh QI Development Programme as well as the Edward Jenner NHS Leadership Academy Programme. Funding has also been secured to deliver further formal QI training from Improvement Cymru. These skills have then been used by the Innovation Fellows when undertaking QI and innovation work.ResultsAs of August 2020, 8/12 (75%) of Innovation fellows completed the Improving Quality Together Welsh QI Development Programme and 5/11 (45%) have completed the Edward Jenner NHS Leadership Academy Programme. 10/12 (83%) feel that their leadership skills have improved since becoming an Innovation Fellow. 11/12 (92%) feel more motivated to undertake QI and innovation since becoming an Innovation Fellow, and 10/12 (83%) feel more motivated to support others undertake QI and innovation since starting the programme. 10/11 (91%) also feel that their leadership experience may better equip them in the planning and management of future COVID challenges.ConclusionsEmpowering junior doctors with leadership responsibilities while also providing mentorship and formal QI training can enhance their leadership skills, motivate them to undertake QI and innovation, and empower them to supervise and mentor others. Other NHS organisations should consider appointing Innovation Fellows in a similar way to Betsi Cadwaladr University Health Board.

Cross-Reactive SARS-CoV-2 Neutralizing Antibodies From Deep Mining of Early Patient Responses.

Passive immunization using monoclonal antibodies will play a vital role in the fight against COVID-19. The recent emergence of viral variants with reduced sensitivity to some current antibodies and vaccines highlights the importance of broad cross-reactivity. This study describes deep-mining of the antibody repertoires of hospitalized COVID-19 patients using phage display technology and B cell receptor (BCR) repertoire sequencing to isolate neutralizing antibodies and gain insights into the early antibody response. This comprehensive discovery approach has yielded a panel of potent neutralizing antibodies which bind distinct viral epitopes including epitopes conserved in SARS-CoV-1. Structural determination of a non-ACE2 receptor blocking antibody reveals a previously undescribed binding epitope, which is unlikely to be affected by the mutations in any of the recently reported major viral variants including B.1.1.7 (from the UK), B.1.351 (from South Africa) and B.1.1.28 (from Brazil). Finally, by combining sequences of the RBD binding and neutralizing antibodies with the B cell receptor repertoire sequencing, we also describe a highly convergent early antibody response. Similar IgM-derived sequences occur within this study group and also within patient responses described by multiple independent studies published previously.

Non-Western interventions for stress reduction and resilience

SUMMARYComplementary and integrative medicine provides safe, low-cost, effective treatments for conditions ranging from everyday stress to post-traumatic stress disorder. The evidence for herbs, nutrients and mind–body practices is growing, despite disproportionately small amounts of financial support compared with funding for expensive pharmaceuticals. The unsustainable cost of conventional treatments, the moral imperative to care for millions of uninsured and the impact of COVID-19 compel us to fully explore known and potential benefits of treatments being used by complementary and integrative practitioners.

The value of stable, comparable and standardised measurement: enabling confidence in decision making for societal challenges

Making decisions that have broad societal and economic impact is extremely hard. This is especially true when the data upon which choices for future action are based are unstable or have uncertain provenance. This letter discusses the benefits of metrology, as the science of measurement, in providing data that is stable, comparable and produced using standardised methods, in enabling greater confidence in the decision-making process. A key part of this increased confidence is via providing input data with reduced uncertainty, thereby decreasing the uncertainty of future predictions. The application of these principles to the two biggest societal challenges currently, COVID-19 and climate change, is discussed, and similarities and differences of approaches highlighted. It is foreseen that the role of metrology in enabling evidence-based decision making will become increasingly more important in future. Formal agreements and memoranda of understanding between the metrology community and the relevant global technical bodies are the best way to improve data quality, reliability and comparability, and therefore the confidence with which decisions can be made. Whilst uncertainties in data may be driven down as technology and metrology improves, they can never be eliminated entirely, and we must accept some level of uncertainty in our decision making.

Distance Management of Spinal Disorders During the COVID-19 Pandemic and Beyond: Evidence-Based Patient and Clinician Guides From the Global Spine Care Initiative.

BACKGROUND: The COVID-19 pandemic has greatly limited patients' access to care for spine-related symptoms and disorders. However, physical distancing between clinicians and patients with spine-related symptoms is not solely limited to restrictions imposed by pandemic-related lockdowns. In most low- and middle-income countries, as well as many underserved marginalized communities in high-income countries, there is little to no access to clinicians trained in evidence-based care for people experiencing spinal pain. OBJECTIVE: The aim of this study is to describe the development and present the components of evidence-based patient and clinician guides for the management of spinal disorders where in-person care is not available. METHODS: Ultimately, two sets of guides were developed (one for patients and one for clinicians) by extracting information from the published Global Spine Care Initiative (GSCI) papers. An international, interprofessional team of 29 participants from 10 countries on 4 continents participated. The team included practitioners in family medicine, neurology, physiatry, rheumatology, psychology, chiropractic, physical therapy, and yoga, as well as epidemiologists, research methodologists, and laypeople. The participants were invited to review, edit, and comment on the guides in an open iterative consensus process. RESULTS: The Patient Guide is a simple 2-step process. The first step describes the nature of the symptoms or concerns. The second step provides information that a patient can use when considering self-care, determining whether to contact a clinician, or considering seeking emergency care. The Clinician Guide is a 5-step process: (1) Obtain and document patient demographics, location of primary clinical symptoms, and psychosocial information. (2) Review the symptoms noted in the patient guide. (3) Determine the GSCI classification of the patient's spine-related complaints. (4) Ask additional questions to determine the GSCI subclassification of the symptom pattern. (5) Consider appropriate treatment interventions. CONCLUSIONS: The Patient and Clinician Guides are designed to be sufficiently clear to be useful to all patients and clinicians, irrespective of their location, education, professional qualifications, and experience. However, they are comprehensive enough to provide guidance on the management of all spine-related symptoms or disorders, including triage for serious and specific diseases. They are consistent with widely accepted evidence-based clinical practice guidelines. They also allow for adequate documentation and medical record keeping. These guides should be of value during periods of government-mandated physical or social distancing due to infectious diseases, such as during the COVID-19 pandemic. They should also be of value in underserved communities in high-, middle-, and low-income countries where there is a dearth of accessible trained spine care clinicians. These guides have the potential to reduce the overutilization of unnecessary and expensive interventions while empowering patients to self-manage uncomplicated spinal pain with the assistance of their clinician, either through direct in-person consultation or via telehealth communication.

Measuring measurement - What is metrology and why does it matter?

Metrology remains a uniquely important endeavour. A sign of its success and robustness as an infra-technology is that it usually goes unnoticed. This means that it is in danger of being under-valued and under-appreciated. The sure-footing that metrology provides to the quality infrastructure will be especially important as the world grapples with the aftereffects of the COVID-19 pandemic, rebuilding global economies and also re-focusing on addressing global grand challenges and exploiting emerging technologies. In this context it is important and timely to re-examine the concept of metrology and how it relates to the quality infrastructure that it serves, but differs to measurement in general. The concept of metrology as 'measuring measurement' is proposed, emphasising the characteristic meta-thought associated with the discipline that distinguishes it from routine measurement.

Exogenous shocks and managerial preparedness: A study of U.S. airlines’ environmental scanning before the onset of the COVID-19 pandemic

Managerial preparedness is a constant concern for firm stakeholders. This concern is exacerbated during times of immense stress brought about by exogenous shocks. In this paper, we analyze the preparedness of U.S. commercial airline management teams to the largest systematic exogenous shock to date, namely the COVID-19 pandemic in 2019 and 2020. We do this by underpinning the paper with theory on environmental scanning and managerial dysfunction and then documenting the signals and actions of management around multiple public health scares. These include the SARS outbreak, the Swine Flu outbreak and the COVID-19 outbreak. Our results, based off of corporate filings with the SEC, is that airline management had multiple “dry runs” before the COVID-19 outbreak that should have lead them to prepare for financially catastrophic scenarios such as the one observed in 2020. Instead, management teams failed to learn from these, and other, prior shocks. Instead, they focused on other, less serious threats while diffusing their financial buffers through dividends and share buybacks.