MAXIMUM n-TIMES COVERAGE FOR VACCINE DESIGN

We introduce the maximum n-times coverage problem that selects k overlays to maximize the summed coverage of weighted elements, where each element must be covered at least n times. We also define the min-cost n-times coverage problem where the objective is to select the minimum set of overlays such that the sum of the weights of elements that are covered at least n times is at least τ. Maximum n-times coverage is a generalization of the multi-set multi-cover problem, is NP-complete, and is not submodular. We introduce two new practical solutions for n-times coverage based on integer linear programming and sequential greedy optimization. We show that maximum n-times coverage is a natural way to frame peptide vaccine design, and find that it produces a pan-strain COVID-19 vaccine design that is superior to 29 other published designs in predicted population coverage and the expected number of peptides displayed by each individual's HLA molecules. © 2022 ICLR 2022 - 10th International Conference on Learning Representationss. All rights reserved.

The Clinical Effectiveness of Dynamic Electronic Tracking and Escalation to Reduce Critical Care Transfers (the Detect Study)

BACKGROUND AND AIM: Physiological surveillance systems significantly reduced adult mortality in two large UK hospitals. In hospitalised children mortality is low, but there may be potential to reduce the morbidity associated with critical deterioration (CD). However, the risk models for adults are unsuitable for use in children because the signs associated with deterioration [heart rate, breathing rate, blood pressure], alter significantly across the age range. The aim is to evaluate whether this technology improves clinical outcomes for in-hospital deterioration, including sepsis in children. METHOD(S): ISRCTN61279068. https://bit.ly/36HtEGF Participants: Paediatric in-patients, aged less than 18 years at a tertiary hospital (240 beds). Intervention(s): Careflow Vitals and Connect app platform configured to incorporate the Alder Hey age-specific Paediatric Early Warning score (PEWS) and modified National Institute of Health and Clinical Excellence (NICE) Sepsis screening. The documentation of vital signs and clinical observations occur at the patient's bedside at intervals determined by the PEWS risk model. PEWS categorised CD risk as low, moderate, high and critical and provided targeted escalation advice and automated alerts to the Nurse in Charge of the shift and the responsible Clinical Teams. Primary Outcome:Emergency transfers to Critical Care (PICU/ HDU). RESULT(S): Prospective data collection baseline year March 2018 - February 2019 compared with 2 years postintervention March 2020-February 2022 (Extended due to COVID). Summary of results in Figure 1. CONCLUSION(S): The absolute number of CD and patients affected reduced by 29%. Associated review of the cases using the Predictability/Preventability framework showed reduction in the late recognition and CD with modifiable factors. (Figure Presented).

The Superhero Scrub Project: Assembling Positive Paediatric Experiences

Aims Throughout the Covid-19 pandemic, several working practices were changed to allow for better infection control awareness and practice. St Richard's Hospital paediatric department adopted the use of medical scrubs as the standard workwear for medical staff. Children frequently find the hospital environment frightening and unfamiliar, and it is well recognised that practices that utilise play and 'fun' are effective in improving patient and parent engagement and outcomes.1 Furthermore, direct communication with the child and engagement of their interests and activities beyond their medical needs is also acknowledged as a critical element of patient centred care.2 The use of more child friendly imagery such as teddy bears or cartoons on medical clothing/devices within paediatrics is well established. The aim of this project was to trial a 'fun' but practical scrubs uniform that children and their parents would recognise and enjoy seeing, with the aim of providing a positive and less threatening experience for the child and to summarise early feedback as a proof of concept. Methods 5 sets of superhero themed scrubs were created, based on the appearances of Marvel's 'Avengers' and were worn as clinical workwear throughout the pandemic period. Verbal feedback from patients, parents and colleagues was documented and analysed for common themes. Results 'I liked Ben/Spiderman! He made me feel HAPPY!' - 8 year old female patient Feedback was positive overall. Patients generally responded positively to the superhero appearance, and frequently expressed excitement at recognising a character. However, this was sometimes short lived depending on the nature of the clinical encounter. For younger patients in particular, painful procedures remained a source of upset. Parents across the paediatric, A&E, maternity and neonatal departments frequently expressed positive sentiments about the scrubs and often made reference to their expectation that children would enjoy the appearance. No specific negative sentiment was directly fed back, however this may reflect withheld judgement and the need for a more anonymised assessment. Similar positive sentiments were fielded from medical and nursing staff across departments, though with occasional concerns expressed about the professionalism of the clothing, especially if there were a scenario of needing to break bad news. An unexpected effect was to cause amusement and anticipation of what outfit would be expected for the duty - which acted as a morale boost of sorts. Conclusion Incorporating familiar character appearances into medical workwear was well received by patients, parents and staff;and may help lessen feelings of a hospital environment seeming threatening to the child. This could benefit rapport, communication and patient outcomes. Scrub patterns are widely available and easily adaptable for different characters, though this is limited by sewing skill, cost and motivation. There are also limitations their use, particularly where the use of 'fun' imagery is emotionally incongruent. (Figure Presented).

Consulting with Children and Parents to Cocreate Resources About Receiving Paediatric Outpatient Parenteral Antimicrobial Therapy (Opat)

Aims We aim to showcase how we engaged with children and their parents via a teleconferencing platform (Zoom) using the power of illustration to trigger their recall of going home on outpatient parenteral antimicrobial therapy (OPAT). This co-creative consultation work was conducted to address the need, identified by children and parents in a previous research study, for enhanced preparation and information about OPAT. Methods Children (n=4) who had received OPAT and their parents (n=4) were invited to participate by clinicians in the OPAT team at the children's tertiary centre. The children were sent specifically designed activity sheets asking them about their experiences in advance of an online activity consultation via Zoom. There was no set schedule for the online activity, instead conversation was triggered by the researchers asking the children about their drawings and responses in their completed activity sheets. Meanwhile, the illustrator listened, shared their screen, utilised the children's drawings and words and created new images that brought to life, in realtime, the experiences children and their parents shared. Children and their parents were in control of the process as they could direct, confirm or alter the drawings that appeared on the screen and ask for text to be added. Results The freely available, co-developed resources include a 3-minute long animation (figure 1) and an information leaflet (figure 2), has been designed by and for children and their parents. Although remote engagement with children has become more commonplace, the use of real-time, co-creation based on children's illustrations and augmented by professional illustration and animation during the online activity is novel. The strengths (e.g. children enjoyed the approach) and limitations (e.g. reliance on stable Wi-Fi) of this approach have been explored. The findings from this consultation aligned with and added depth to understanding the experiences of children and parents about being at home on OPAT. Link to animation: https://www.youtube.com/watch? v=JERVuqmLLDM Link to information leaflet: https://figshare.edgehill.ac.uk/ articles/figure/Things-you-might-like-to-know-about-having- your-medicine-at-home-information-leaflet-OPAT-/ 19180895/1 872 Figure 1 872 Figure 2 Conclusion The COVID-19 pandemic has had a profound impact on the way consultation activities are conducted. This illustration driven, virtual consultation method with children receiving OPAT and their parents was successful and allowed the co-creation of free resources for other children and parents to use. Rather than constrain what was done, using virtual methods meant that children and their parents were able to engage with and co-create ideas for resources from the comfort of their own homes.

Using Neural Networks to Model the Spread of COVID-19

The spread of the novel coronavirus across the world in 2020 exposed the tenuous nature of hospital capacity and medical resource supply lines. Being able to anticipate surge events days before they hit an area would allow healthcare workers to pivot and prepare, critically expanding capacity and adjusting to resource loads. This work aims to enable advanced healthcare planning by providing adaptive forecasts into short range COVID-19 outbreaks and surge events. Here, we present a novel method to predict the spread of COVID-19 by using creative neural network architectures, especially convolutional and LSTM layers. Our goal was to create a generalizable method or model to predict disease spread on a county-level granularity. Importantly, we found that by using an adaptive neural network model with a frequent refresh rate, we were able to outperform simple feed forward estimation methods to predict county level new case counts on a daily basis. We also show the capabilities of neural network architectures by comparing performance on different sizes of training data and geographic inputs. Our results indicate that neural networks are well suited to dynamically modeling the spread of COVID-19 on a county-level basis, but that cultural and/or geographic differences in regions prevent the portability of fully-trained models. © 2022 IEEE.

Does the Prosperity of a Country Play a Role in COVID-19 Outcomes?

OBJECTIVE: This study aims to clarify the association between prosperity and the coronavirus disease (COVID-19) outcomes and its impact on the future management of pandemics. METHODS: This is an observational study using information from 2 online registries. The numbers of infected individuals and deaths and the prosperity rank of each country were obtained from worldometer.info and the Legatum Institute's Prosperity Index, respectively. RESULTS: There is a combination of countries with high and low prosperity on the list of COVID-19-infected countries. The risk of the virus pandemic seems to be more extensive in countries with high prosperity. A Spearman's rho test confirmed a significant correlation between prosperity, the number of COVID-19 cases, and the number of deaths at the 99% level. CONCLUSION: New emerging pandemics affect all nations. In order to increase the likelihood of successfully managing future events, it is important to consider preexisting health security, valid population-based management approaches, medical decision-making, communication, continuous assessment, triage, treatment, early and complete physical distancing strategies, and logistics. These elements cannot be taught on-site and on occasion. There is a need for innovative and regular educational activities for all stakeholders committed to safeguarding our future defense systems concerning diagnostic, protection, treatment, and rehabilitation in pandemics, as well as other emergencies.

COVID-19 in CHILDREN: WORSENING OUTCOMES during DELTA VARIANT WAVE

Background: Pediatric cases of COVID-19 surged in the summer/fall of 2021 coinciding with the SARS-CoV-2 Delta variant. It is unclear whether the Delta variant caused more severe illness among pediatric patients. We leveraged the Children and COVID-19 in Colorado database to determine whether differences exist in demographics, underlying comorbidities, and outcomes among children requiring hospital admission due to the SARS-CoV-2 Delta variant vs. wild type virus. Methods: We performed a retrospective review of children <21 years with symptomatic COVID-19 and detectable SARS-CoV-2 NAAT hospitalized at Children's Hospital Colorado during pre-Delta (Mar-Nov 2020) and Delta (Jun-Sep 2021) periods. We compared variables using Fisher's exact or Pearson's chi square tests for categorical variables and Wilcoxon rank sum tests for continuous variables. Results: There were 119 children hospitalized with symptomatic COVID-19 during the pre-Delta and 137 in the Delta period. There was a slight male predominance in both periods. Children hospitalized during the Delta period were younger, with median (interquartile range) age of 5.9 (1.0-14.5) vs. 12.2 (1.5-16.9) years, p=0.02;and were less likely to identify as Hispanic and Spanish-speaking, compared to the pre-Delta period (Table). There was a trend toward decreasing proportions of hospitalized children with underlying comorbidities in the Delta vs. pre-Delta period (59.1% vs. 69.8%;p=0.07). The most prevalent types of comorbidities were similar between periods;but the proportion of hospitalized immunocompromised patients was lower in the Delta vs. pre-Delta period (p=0.005). Half of all children were overweight/obese in both periods. Similar proportions of hospitalized children required respiratory support in both periods, but more children required intensive care in the Delta vs. pre-Delta periods (36.5% vs. 23.5%, p=0.03). Conclusion: Children hospitalized with the Delta variant of COVID-19 were younger, less likely to be Hispanic, and had fewer comorbidities than children hospitalized with wild type SARS-CoV-2. Children hospitalized with the Delta variant were more likely to require ICU admission compared to children hospitalized with wild type SARS-CoV-2, which may indicate increased severity of the Delta variant in the pediatric population. Close monitoring of pediatric outcomes is needed as new SARS-CoV-2 variants emerge.

Outreach and Scientific Results with the Largest Network of Backyard Astronomers

The Unistellar network is today made of more 5,000 digital telescopes—the eVscope, the eQuinox, and the recently released eVscope 2. These powerful, easy-to-use, smart devices allow backyard astronomers to enjoy the dark sky while also contributing to scientific projects in partnership with the SETI Institute. We believe that science can reap an immense harvest from continuous observations of the night sky using these eVscopes while we also give laypeople, students, and teachers the opportunity to experience the thrill of the next frontier, space exploration. Here we present outreach activities organized by our network, including on-line events made necessary by COVID-19 restrictions in 2020. This paper includes a discussion of our education programs, which aim to connect to our network’s teachers with students from underrepresented groups in the US who are enrolled in community colleges. Finally, we will describe several scientific results generated by our network related to the study of exoplanets, asteroids, and comets. Copyright © 2021 by the International Astronautical Federation (IAF). All rights reserved.

PREVALENCE AND IMPACT OF FRAILTY IN PATIENTS HOSPITALISED WITH COVID-19. THE SALFORD EXPERIENCE IN WAVES 1 AND 2

IntroductionThe COVID-19 pandemic has had an extensive impact on the frail older population, with significant rates of COVID-related hospital admissions and deaths amongst this vulnerable group. There is little evidence of frailty prevalence amongst patients hospitalised with COVID-19, nor the impact of frailty on their survival. MethodsProspective observational study of all consecutive patients admitted to Salford Royal NHS Foundation (SRFT) Trust between 27th February and 28th April 2020 (wave 1), and 1st October to 10th November 2020 (wave 2) with a diagnosis of COVID-19. The primary endpoint was in-hospital mortality. Patient demographics, co-morbidities, admission level disease severity (estimated with CRP) and frailty (using the Clinical Frailty Scale, score 1–3 = not frail, score 4–9 = frail) were collected. A Cox proportional hazards regression model was used to assess the time to mortality. ResultsA total of 693 (N = 429, wave 1;N = 264, wave 2) patients were included, 279 (N = 180, 42%, wave 1;N = 104, 38%, wave 2) were female, and the median age was 72 in wave 1 and 73 in wave 2. 318 (N = 212, 49%, wave 1;N = 106, 39%, wave 2) patients presenting were frail. There was a reduction in mortality in wave 2, adjusted Hazard ratio (aHR) = 0.60 (95%CI 0.44–0.81;p = 0.001). There was an association between frailty and mortality aHR = 1.57 (95%CI 1.09–2.26;p = 0.015). ConclusionFrailty is highly prevalent amongst patients of all ages admitted to SRFT with COVID-19. Higher scores of frailty are associated with increased mortality.

Increased care at discharge from COVID-19: The association between pre-admission frailty and increased care needs after hospital discharge; a multicentre European observational cohort study.

BACKGROUND: The COVID-19 pandemic has placed significant pressure on health and social care. Survivors of COVID-19 may be left with substantial functional deficits requiring ongoing care. We aimed to determine whether pre-admission frailty was associated with increased care needs at discharge for patients admitted to hospital with COVID-19. METHODS: Patients were included if aged over 18 years old and admitted to hospital with COVID-19 between 27 February and 10 June 2020. The Clinical Frailty Scale (CFS) was used to assess pre-admission frailty status. Admission and discharge care levels were recorded. Data were analysed using a mixed-effects logistic regression adjusted for age, sex, smoking status, comorbidities, and admission CRP as a marker of severity of disease. RESULTS: Thirteen hospitals included patients: 1671 patients were screened, and 840 were excluded including, 521 patients who died before discharge (31.1%). Of the 831 patients who were discharged, the median age was 71 years (IQR, 58-81 years) and 369 (44.4%) were women. The median length of hospital stay was 12 days (IQR 6-24). Using the CFS, 438 (47.0%) were living with frailty (≥ CFS 5), and 193 (23.2%) required an increase in the level of care provided. Multivariable analysis showed that frailty was associated with an increase in care needs compared to patients without frailty (CFS 1-3). The adjusted odds ratios (aOR) were as follows: CFS 4, 1.99 (0.97-4.11); CFS 5, 3.77 (1.94-7.32); CFS 6, 4.04 (2.09-7.82); CFS 7, 2.16 (1.12-4.20); and CFS 8, 3.19 (1.06-9.56). CONCLUSIONS: Around a quarter of patients admitted with COVID-19 had increased care needs at discharge. Pre-admission frailty was strongly associated with the need for an increased level of care at discharge. Our results have implications for service planning and public health policy as well as a person's functional outcome, suggesting that frailty screening should be utilised for predictive modelling and early individualised discharge planning.

Nosocomial COVID-19 infection: examining the risk of mortality. The COPE-Nosocomial Study (COVID in Older PEople).

BACKGROUND: Hospital admissions for non-coronavirus disease 2019 (COVID-19) pathology have decreased significantly. It is believed that this may be due to public anxiety about acquiring COVID-19 infection in hospital and the subsequent risk of mortality. AIM: To identify patients who acquire COVID-19 in hospital (nosocomial COVID-19 infection (NC)) and their risk of mortality compared to those with community-acquired COVID-19 (CAC) infection. METHODS: The COPE-Nosocomial Study was an observational cohort study. The primary outcome was the time to all-cause mortality (estimated with an adjusted hazard ratio (aHR)), and secondary outcomes were day 7 mortality and the time-to-discharge. A mixed-effects multivariable Cox's proportional hazards model was used, adjusted for demographics and comorbidities. FINDINGS: The study included 1564 patients from 10 hospital sites throughout the UK, and one in Italy, and collected outcomes on patients admitted up to April 28th, 2020. In all, 12.5% of COVID-19 infections were acquired in hospital; 425 (27.2%) patients with COVID died. The median survival time in NC patients was 14 days compared with 10 days in CAC patients. In the primary analysis, NC infection was associated with lower mortality rate (aHR: 0.71; 95% confidence interval (CI): 0.51-0.98). Secondary outcomes found no difference in day 7 mortality (adjusted odds ratio: 0.79; 95% CI: 0.47-1.31), but NC patients required longer time in hospital during convalescence (aHR: 0.49, 95% CI: 0.37-0.66). CONCLUSION: The minority of COVID-19 cases were the result of NC transmission. No COVID-19 infection comes without risk, but patients with NC had a lower risk of mortality compared to CAC infection; however, caution should be taken when interpreting this finding.

A Coronavirus (COVID-19) Triage Framework for (Sub)National Public-Private Partnership (PPP) Programs

Around the world, countries are struggling to address the immediate and long-term impacts of the novel coronavirus (COVID-19) pandemic on their (sub)national public-private partnership (PPP) programs. Burdened with the real possibility of widespread project failures and constrained budgets, governments are searching for ways to prioritize projects in need of relief and bolster post-pandemic recovery plans. To meet this need, this article conceptualizes a triage system for PPP programs based on five categories: (1) projects without a need for economic stimulus (blue);(2) projects experiencing minor economic/financial losses (green);(3) projects needing temporary/stop-gap support or restructuring (yellow);(4) projects unable to survive without significant economic relief (red);and (5) projects that cannot survive, even with government intervention (black). This research also stresses the importance of launching and sustaining a crisis command center to support PPP triage decisions and encourages PPP stakeholders to collectively craft win-win solutions for post-pandemic recovery efforts.