Digital Manufacturing on a Shoestring - Low-Cost Digital Solutions for Manufacturing SMEs: Priority Solutions Areas

The aim of this paper is to provide an understanding of the priority digital solution areas for manufacturing SMEs. In this study, we examined the digitalisation preferences of 128 SMEs working with a predefined catalogue of 59 digital solution areas. This catalogue of digital solutions has previously been introduced in a companion whitepaper [18]. Out of all participants in the study, 86% ranked one of the top 5 items as a key priority for their business and 98% of respondents ranked one of the top 15 as priority. This contribution can help increase accessibility to digitalisation for manufacturing SMEs by allowing small manufacturers to focus on areas of immediate benefit and solution developers to concentrate efforts in these priority areas.This work was supported by the Engineering and Physical Sciences Research Council [grant number EPSRC: EP/R032777/1

Digital Manufacturing on a Shoestring - Low-Cost Digital Solutions for Manufacturing SMEs: A Catalogue of Digital Solution Areas

The aim of this paper is to present a catalogue comprising a set of digital solution areas associated with operational challenges that are relevant to a majority of manufacturing small to medium sized enterprises (SMEs). The working catalogue has been developed in consultation with over 100 manufacturing SMEs. The working catalogue describes 59 solution areas identified to the end of 2020. Out of all participants in the study, 86% ranked one of the top 5 items in the catalogue as a key priority for their business. These findings can help increase accessibility to digitalisation for manufacturing SMEs.This work was supported by the Engineering and Physical Sciences Research Council [grant number EPSRC: EP/R032777/1

Tracing ingestion of 'novel' foods in UK diets for possible health surveillance: a feasibility study

Objective: To investigate the feasibility of using commercially available data on household food consumption to carry out food and nutritional surveillance. Design: Taylor Nelson Sofres (TNS) collects information on foods brought home for consumption among a representative quota sample of the British population. In total, 33 177 households and 105 667 individuals provided data between 1991 and 2000. These were used to investigate sociodemographic, geographical and temporal trends in purchase patterns of the main macronutrients and four groups of marker products. Results: Sociodemographic characteristics of the TNS sample were broadly consistent with those of the British population. Estimated energy intakes were slightly low (1667 +/- 715 kcal) in comparison with other national data. However, percentage energy contributions were consistent with national trends: e.g. consumption of alcohol in the home increased between 1991 and 2000 with higher intakes among more affluent households, while fat intakes decreased slightly over the same period. Significant temporal, geographic and socio-economic trends were found for all nutrients (P < 0.0001). Intakes of marker products were sparse (purchased by < 4% of households), but significant variations were detected in the proportion of households purchasing some or all of the marker products across temporal, geographic and socio-economic strata. Conclusions: A prospective nutrient surveillance system could be used to trace consumption patterns of foods or nutrients to inform nutritional surveillance. However, existing data sources would require a number of modifications to increase their suitability for such a project. Increasing surveillance to consider ingredients would require the development of a central coding system, with electronically linked barcode, ingredient and nutrient information

Public Health Directives in a Pandemic: Paradoxical Messages for Domestic Abuse Victims in Four Countries

When the COVID-19 pandemic manifested urgent concerns were raised around the globe about the increased risk that public health restrictions could pose for victims of domestic abuse. Governments, NGOs and community services swiftly responded to convey the message that services for victims were operational and restrictions did not apply to those fleeing harm. This paper reports on the various approaches used to communicate this public health messaging during COVID-19, further highlighting strengths and learning which could inform future crises messaging. It utilises data gathered through a rapid review and mapping of policy and practice initiatives across 4 high-middle income countries: UK, Australia, South Africa and Ireland. Four themes were identified: (1) Top-down: National media messaging; (2) Top-down: Political leadership; (3) Traditional media vs. social media and (4) Bottom-up messaging: Localised, community-based messaging. It was found that a strong, clear top-down stance on domestic abuse was perceived as beneficial during COVID-19. However, a stronger focus on evaluation, reach and impact, particularly for minority groups may be required. Newer forms of media were shown to have potential in conveying messaging to minority groups. Community and grassroots organizations demonstrated their experiential knowledge in reaching target audiences. Harnessing this expertise for future crises messaging may be valuable

Circular economy inspired imaginaries for sustainable innovations

In this chapter, Narayan and Tidström draw on the concept of imaginaries to show how Circular Economy (CE) can facilitate values that enable sustainable innovation. Innovation is key for sustainability, however, understanding and implementing sustainable innovation is challenging, and identifying the kind of actions that could direct sustainable innovations is important. The findings of this study indicate that CE-inspired imaginaries enable collaboration and by relating such imaginaries to common and shared social and cultural values, intermediaries could motivate actors into taking actions that contribute to sustainable innovation.fi=vertaisarvioitu|en=peerReviewed

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication