Search

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jebo.2004.07.021 Byline: R. Guimera (a), L. Danon (b), A. Diaz-Guilera (b), F. Giralt (c), A. Arenas (d) Keywords: Email network; Informal charts; Complex networks Abstract: The formal chart of an organization is intended to prescribe how employees interact. However, ties between individuals arise for personal, political, and cultural reasons. The characterization of the structure of such informal networks behind the formal chart is a key element for successful management. We surmise that the exchange of e-mails between individuals in organizations reveals how people interact and therefore provides a map of the real network structure behind the formal chart. We propose a methodology that allows extraction of relevant information about the community structure of an organization from the network of e-mail interactions between its employees. Author Affiliation: (a) Department of Chemical Engineering, Northwestern University, Evanston, IL, USA (b) Departament de Fisica Fonamental, Universitat de Barcelona, Barcelona, Catalonia, Spain (c) Departament d'Enginyeria Quimica, Universitat Rovira i Virgili, Tarragona, Catalonia, Spain (d) Departament d'Enginyeria Informatica i Matematiques, Universitat Rovira i Virgili, Tarragona, Catalonia, Spain Article History: Received 2 November 2003; Accepted 21 July 2004

Background: In the past several decades, conflicting discourses have coexisted in the field of intersex studies, including the pathologizing discourse of the biomedical disciplines and the affirmative, subjective psychosocial discourse of people born with intersex bodies and their advocates. Intersex activists call for a positive discourse and a humanistic healthcare approach that accepts and protects intersex bodily autonomy and change the continuing harmful, traumatic treatments aimed at normalizing variations of sex characteristics (VSC). Methods: We created a collaborative German-Israeli action study, in with 30 health care professionals, intersex activists and scholars from Israel and Germany, were gathered to learn different perspectives on intersexuality, interact and work together on projects aim to improve the care for intersex people and families. Results: The participants created different collaborative projects, including ‘‘intersex workshops’’ for caregivers and professionals in Israel and Germany; unique materials for raising an awareness, e.g., booklets on intersex bodies with a positive and affirmative approach and language and an article for health care within the ultraorthodox Jewish community; parents’ groups and implementation of programs that aim to build bridges between biomedical professionals, caregivers, parents, and intersex people in Israel and Germany. Conclusions: The participants increased their knowledge and awareness of and sensitivity to intersex issues, and implemented these in their daily work and practices. The participants acknowledged the differences between the countries, especially in relation to the heightened Israeli use of assisted reproductive technology, which effect on the treatment practices, early genetic diagnosis and the preventive medical attitude. In Germany, more activism for intersex human rights and significant laws which regulate the medical treatment practices. [ABSTRACT FROM AUTHOR]

Background: In the event of a release of a pathogen such as smallpox, which is human-to-human transmissible and has high associated mortality, a key question is how best to deploy containment and control strategies. Given the general uncertainty surrounding this issue, mathematical modelling has played an important role in informing the likely optimal response, in particular defining the conditions under which mass-vaccination would be appropriate. In this paper, we consider two key questions currently unanswered in the literature: firstly, what is the optimal spatial scale for intervention; and secondly, how sensitive are results to the modelling assumptions made about the pattern of human contacts?Methods: Here we develop a novel mathematical model for smallpox that incorporates both information on individual contact structure (which is important if the effects of contact tracing are to be captured accurately) and large-scale patterns of movement across a range of spatial scales in Great Britain.Results: Analysis of this model confirms previous work suggesting that a locally targeted 'ring' vaccination strategy is optimal, and that this conclusion is actually quite robust for different socio-demographic and epidemiological assumptions.Conclusions: Our method allows for intuitive understanding of the reasons why national mass vaccination is typically predicted to be suboptimal. As such, we present a general framework for fast calculation of expected outcomes during the attempted control of diverse emerging infections; this is particularly important given that parameters would need to be interactively estimated and modelled in any release scenario. [ABSTRACT FROM AUTHOR]

Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Catherine Hyams reports financial support was provided by Pfizer Inc. Adam Finn reports financial support was provided by Pfizer. Adam Finn reports a relationship with Joint Committee on Vaccination and Immunization that includes: board membership. CH is Principal Investigator of the AvonCAP study which is an investigator-led University of Bristol study funded by Pfizer and has previously received support from the NIHR in an Academic Clinical Fellowship. JO and LD are Co-Investigators on the AvonCAP Study. AF is a member of the Joint Committee on Vaccination and Immunization (JCVI) and, until December 2022 was chair of the World Health Organization European Technical Advisory Group of Experts on Immunization (ETAGE) committee. In addition to receiving funding from Pfizer as Chief Investigator of this study, he leads another project investigating transmission of respiratory bacteria in families jointly funded by Pfizer and the Gates Foundation. The other authors have no relevant conflicts of interest to declare. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Lower Respiratory Tract Infections (LRTI) pose a serious threat to older adults but may be underdiagnosed due to atypical presentations. Here we assess LRTI symptom profiles and syndromic (symptom-based) case ascertainment in older (≥ 65y) as compared to younger adults (< 65y)., Methods: We included adults (≥ 18y) with confirmed LRTI admitted to two acute care Trusts in Bristol, UK from 1st August 2020- 31st July 2022. Logistic regression was used to assess whether age ≥ 65y reduced the probability of meeting syndromic LRTI case definitions, using patients' symptoms at admission. We also calculated relative symptom frequencies (log-odds ratios) and evaluated how symptoms were clustered across different age groups., Results: Of 17,620 clinically confirmed LRTI cases, 8,487 (48.1%) had symptoms meeting the case definition. Compared to those not meeting the definition these cases were younger, had less severe illness and were less likely to have received a SARS-CoV-2 vaccination or to have active SARS-CoV-2 infection. Prevalence of dementia/cognitive impairment and levels of comorbidity were lower in this group. After controlling for sex, dementia and comorbidities, age ≥ 65y significantly reduced the probability of meeting the case definition (aOR = 0.67, 95% CI:0.63-0.71). Cases aged ≥ 65y were less likely to present with fever and LRTI-specific symptoms (e.g., pleurisy, sputum) than younger cases, and those aged ≥ 85y were characterised by lack of cough but frequent confusion and falls., Conclusions: LRTI symptom profiles changed considerably with age in this hospitalised cohort. Standard screening protocols may fail to detect older and frailer cases of LRTI based on their symptoms., (© 2024. The Author(s).)

Multiplex panel tests identify many individual pathogens at once, using a set of component tests. In some panels the number of components can be large. If the panel is detecting causative pathogens for a single syndrome or disease then we might estimate the burden of that disease by combining the results of the panel, for example determining the prevalence of pneumococcal pneumonia as caused by many individual pneumococcal serotypes. When we are dealing with multiplex test panels with many components, test error in the individual components of a panel, even when present at very low levels, can cause significant overall error. Uncertainty in the sensitivity and specificity of the individual tests, and statistical fluctuations in the numbers of false positives and false negatives, will cause large uncertainty in the combined estimates of disease prevalence. In many cases this can be a source of significant bias. In this paper we develop a mathematical framework to characterise this issue, we determine expressions for the sensitivity and specificity of panel tests. In this we identify a counter-intuitive relationship between panel test sensitivity and disease prevalence that means panel tests become more sensitive as prevalence increases. We present novel statistical methods that adjust for bias and quantify uncertainty in prevalence estimates from panel tests, and use simulations to test these methods. As multiplex testing becomes more commonly used for screening in routine clinical practice, accumulation of test error due to the combination of large numbers of test results needs to be identified and corrected for., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CH is Principal Investigator and AF is the Chief Investigator of the AvonCAP study which is an investigator-led University of Bristol study funded by Pfizer https://www.bristol.ac.uk/translational-health-sciences/research/bcvc/research/avoncap-study/. RC, AC, GQ, GO, RK, and LD also receive research funding from Pfizer via the AvonCAP study. AF leads another project investigating transmission of respiratory bacteria in families jointly funded by Pfizer and the Gates Foundation. AF is a member of the Joint Committee on Vaccination and Immunization (JCVI) pneumococcal subcommittee. Funding for the AvonCAP study was provided by Pfizer, however, the manuscript development and the analysis that is the subject of this manuscript were conducted independently of the AvonCAP study and Pfizer., (Copyright: © 2024 Challen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Despite significant global morbidity associated with respiratory infection, there is a paucity of data examining the association between severity of non-SARS-CoV-2 respiratory infection and blood group. We analysed a prospective cohort of adults hospitalised in Bristol, UK, from 1 August 2020 to 31 July 2022, including patients with acute respiratory infection (pneumonia [n = 1934] and non-pneumonic lower respiratory tract infection [NP-LRTI] [n = 1184]), a negative SARS-CoV-2 test and known blood group status. The likelihood of cardiovascular complication, survival and hospital admission length was assessed using regression models with group O and RhD-negative status as reference groups. Group A and RhD-positive were over-represented in both pneumonia and NP-LRTI compared to a first-time donor population (p < 0.05 in all); contrastingly, group O was under-represented. ABO group did not influence cardiovascular complication risk; however, RhD-positive patients with pneumonia had a reduced odds ratio (OR) for cardiovascular complications (OR = 0.77 [95% CI = 0.59-0.98]). Compared to group O, group A individuals with NP-LRTI were more likely to be discharged within 60 days (hazard ratio [HR] = 1.17 [95% CI = 1.03-1.33]), while group B with pneumonia was less likely (HR = 0.8 [95% CI = 0.66-0.96]). This analysis provides some evidence that blood group status may influence clinical outcome following respiratory infection, with group A having increased risk of hospitalisation and RhD-positive patients having reduced cardiovascular complications., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

BackgroundUnderstanding the relative vaccine effectiveness (rVE) of new COVID-19 vaccine formulations against SARS-CoV-2 infection is a public health priority. A precise analysis of the rVE of monovalent and bivalent boosters given during the 2022 spring-summer and autumn-winter campaigns, respectively, in a defined population remains of interest.AimWe assessed rVE against hospitalisation for the spring-summer (fourth vs third monovalent mRNA vaccine doses) and autumn-winter (fifth BA.1/ancestral bivalent vs fourth monovalent mRNA vaccine dose) boosters.MethodsWe performed a prospective single-centre test-negative design case-control study in ≥ 75-year-old people hospitalised with COVID-19 or other acute respiratory disease. We conducted regression analyses controlling for age, sex, socioeconomic status, patient comorbidities, community SARS-CoV-2 prevalence, vaccine brand and time between baseline dose and hospitalisation.ResultsWe included 682 controls and 182 cases in the spring-summer booster analysis and 572 controls and 152 cases in the autumn-winter booster analysis. A monovalent mRNA COVID-19 vaccine as fourth dose showed 46.6% rVE (95% confidence interval (CI): 13.9-67.1) vs those not fully boosted. A bivalent mRNA COVID-19 vaccine as fifth dose had 46.7% rVE (95% CI: 18.0-65.1), compared with a fourth monovalent mRNA COVID-19 vaccine dose.ConclusionsBoth fourth monovalent and fifth BA.1/ancestral mRNA bivalent COVID-19 vaccine doses demonstrated benefit as a booster in older adults. Bivalent mRNA boosters offered similar protection against hospitalisation with Omicron infection to monovalent mRNA boosters given earlier in the year. These findings support immunisation programmes in several European countries that advised the use of BA.1/ancestral bivalent booster doses.

Objectives: To determine whether acute exacerbations of chronic obstructive pulmonary disease (AECOPD) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have worse outcomes than AECOPD caused by other infectious agents or non-infective AECOPD (NI-COPD)., Design: A two-hospital prospective cohort study of adults hospitalised with acute respiratory disease. We compared outcomes with AECOPD and a positive test for SARS-CoV-2 (n = 816), AECOPD triggered by other infections (n = 3038) and NI-COPD (n = 994). We used multivariable modelling to adjust for potential confounders and assessed variation by seasons associated with different SARS-CoV-2 variants., Setting: Bristol UK, August 2020-May 2022., Participants: Adults (≥18 y) hospitalised with AECOPD., Main Outcome Measures: We determined the risk of positive pressure support, longer hospital admission and mortality following hospitalisation with AECOPD due to non-SARS-CoV-2 infection compared with SARS-CoV-2 AECOPD and NI-COPD., Results: Patients with SARS-CoV-2 AECOPD, in comparison to non-SARS-CoV-2 infective AECOPD or NI-COPD, more frequently required positive pressure support (18.5% and 7.5% vs. 11.7%, respectively), longer hospital stays (median [interquartile range, IQR]: 7 [3-15] and 5 [2-10] vs. 4 [2-9] days, respectively) and had higher 30-day mortality (16.9% and 11.1% vs. 5.9%, respectively) (all p  < 0.001). In adjusted analyses, SARS-CoV-2 AECOPD was associated with a 55% (95% confidence interval [95% CI]: 24-93), 26% (95% CI: 15-37) and 35% (95% CI: 10-65) increase in the risk of positive pressure support, hospitalisation length and 30-day mortality, respectively, relative to non-SARS-CoV-2 infective AECOPD. The difference in risk remained similar during periods of wild-type, Alpha and Delta SARS-CoV-2 strain dominance, but diminished during Omicron dominance., Conclusions: SARS-CoV-2-related AECOPD had worse patient outcomes compared with non-SARS-CoV-2 AECOPD or NI-AECOPD, although the difference in risks was less pronounced during Omicron dominance.

Rationale: Streptococcus pneumoniae epidemiology is changing in response to vaccination and some data suggest that empyema incidence is increasing. However, differences exist between the UK and US studies. We describe trends in the clinical phenotype of adult pneumococcal pleural infection, including simple parapneumonic effusions (SPE) in the pneumococcal conjugate vaccination (PCV) era., Objectives: To determine whether there were differences in pneumococcal disease presentation and severity associated with pleural infection., Methods: A retrospective cohort study, all adults ≥16 years admitted to three large UK hospitals, 2006-2018 with pneumococcal disease. 2477 invasive pneumococcal cases were identified: 459 SPE and 100 pleural infection cases. Medical records were reviewed for each clinical episode. Serotype data were obtained from the UK Health Security Agency national reference laboratory., Results: Incidence increased over time, including non-PCV-serotype disease. PCV7-serotype disease declined following paediatric PCV7 introduction, but the effect of PCV13 was less apparent as disease caused by the additional six serotypes plateaued with serotypes 1 and 3 causing such parapneumonic effusions from 2011 onwards.Patients with pleural infection had a median survival 468 days (95% CI 340 to 590) vs 286 days (95% CI 274 to 335) in those with SPE. Pleural infection associated with frank pus had lower 90-day mortality than pleural infection without pus (0% vs 29%, p<0.0001). 90-day mortality could be predicted by baseline increased RAPID (Renal, Age, Purulence, Infection source, and Dietary factors) score (HR 15.01, 95% CI 1.24 to 40.06, p=0.049)., Conclusions: Pneumococcal infection continues to cause severe disease despite the introduction of PCVs. The predominance of serotype 1 and 3 in this adult UK cohort is in keeping with previous studies in paediatric and non-UK studies. Rising non-PCV serotype disease and limited impact of PCV13 on cases caused by serotypes 1 and 3 offset the reductions in adult pneumococcal parapneumonic effusion disease burden observed following the introduction of the childhood PCV7 programme., Competing Interests: Competing interests: CH is the principal investigator of the AvonCAP study which is an investigator-led University of Bristol study funded by Pfizer. AF is a member of the Joint Committee on Vaccination and Immunization (JCVI) and chair of the World Health Organization European Technical Advisory Group of Experts on Immunization (ETAGE) committee. In addition to receiving funding from Pfizer as chief investigator of this study, he leads another project investigating transmission of respiratory bacteria in families jointly funded by Pfizer and the Gates Foundation., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: There is an urgent public health need to evaluate disease severity in adults hospitalised with Delta and Omicron SARS-CoV-2 variant infections. However, limited data exist assessing severity of disease in adults hospitalised with Omicron SARS-CoV-2 infections, and to what extent patient-factors, including vaccination, age, frailty and pre-existing disease, affect variant-dependent disease severity., Methods: A prospective cohort study of adults (≥18 years of age) hospitalised with acute lower respiratory tract disease at acute care hospitals in Bristol, UK conducted over 10-months. Delta or Omicron SARS-CoV-2 infection was defined by positive SARS-CoV-2 PCR and variant identification or inferred by dominant circulating variant. We constructed adjusted regression analyses to assess disease severity using three different measures: FiO 2 >28% (fraction inspired oxygen), World Health Organization (WHO) outcome score >5 (assessing need for ventilatory support), and hospital length of stay (LOS) >3 days following admission for Omicron or Delta infection., Findings: Independent of other variables, including vaccination, Omicron variant infection in hospitalised adults was associated with lower severity than Delta. Risk reductions were 58%, 67%, and 16% for supplementary oxygen with >28% FiO 2 [Relative Risk (RR) = 0.42 (95%CI: 0.34-0.52), P  < 0.001], WHO outcome score >5 [RR = 0.33 (95%CI: 0.21-0.50), P  < 0.001], and to have had a LOS > 3 days [RR = 0.84 (95%CI: 0.76-0.92), P  < 0.001]. Younger age and vaccination with two or three doses were also independently associated with lower COVID-19 severity., Interpretation: We provide reassuring evidence that Omicron infection results in less serious adverse outcomes than Delta in hospitalised patients. Despite lower severity relative to Delta, Omicron infection still resulted in substantial patient and public health burden and an increased admission rate of older patients with Omicron which counteracts some of the benefit arising from less severe disease., Funding: AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer., Competing Interests: CH is Principal Investigator of the AvonCAP study which is an investigator-led University of Bristol study funded by Pfizer and has previously received support from the NIHR in an Academic Clinical Fellowship. JO is a Co-Investigator on the AvonCAP Study. AF is a member of the Joint Committee on Vaccination and Immunization (JCVI) and chair of the World Health Organization European Technical Advisory Group of Experts on Immunization (ETAGE) committee. In addition to receiving funding from Pfizer as Chief Investigator of this study, he leads another project investigating transmission of respiratory bacteria in families jointly funded by Pfizer and the Gates Foundation. LD, RC are members of SPI-M-O subgroups of SAGE and are also partly funded through AvonCAP. LD is a Co-Investigator of the AvonCAP study and has also received funding from Pfizer, UKRI and UKHSA for unrelated projects. EB, JS, JN, SG, GE, LJ, BG, and JMM are employees of Pfizer, Inc and may hold stock or stock options. The other authors have no relevant conflicts of interest to declare., (© 2022 The Author(s).)

Background: Predicting the likely size of future SARS-CoV-2 waves is necessary for public health planning. In England, voluntary "plan B" mitigation measures were introduced in December 2021 including increased home working and face coverings in shops but stopped short of restrictions on social contacts. The impact of voluntary risk mitigation behaviours on future SARS-CoV-2 burden is unknown., Methods: We developed a rapid online survey of risk mitigation behaviours ahead of the winter 2021 festive period and deployed in two longitudinal cohort studies in the UK (Avon Longitudinal Study of Parents and Children (ALSPAC) and TwinsUK/COVID Symptom Study (CSS) Biobank) in December 2021. Using an individual-based, probabilistic model of COVID-19 transmission between social contacts with SARS-CoV-2 Omicron variant parameters and realistic vaccine coverage in England, we predicted the potential impact of the SARS-CoV-2 Omicron wave in England in terms of the effective reproduction number and cumulative infections, hospital admissions and deaths. Using survey results, we estimated in real-time the impact of voluntary risk mitigation behaviours on the Omicron wave in England, if implemented for the entire epidemic wave., Results: Over 95% of survey respondents (N ALSPAC  = 2686 and N Twins  = 6155) reported some risk mitigation behaviours, with vaccination and using home testing kits reported most frequently. Less than half of those respondents reported that their behaviour was due to "plan B". We estimate that without risk mitigation behaviours, the Omicron variant is consistent with an effective reproduction number between 2.5 and 3.5. Due to the reduced vaccine effectiveness against infection with the Omicron variant, our modelled estimates suggest that between 55% and 60% of the English population could be infected during the current wave, translating into between 12,000 and 46,000 cumulative deaths, depending on assumptions about severity and vaccine effectiveness. The actual number of deaths was 15,208 (26 November 2021-1 March 2022). We estimate that voluntary risk reduction measures could reduce the effective reproduction number to between 1.8 and 2.2 and reduce the cumulative number of deaths by up to 24%., Conclusions: Predicting future infection burden is affected by uncertainty in disease severity and vaccine effectiveness estimates. In addition to biological uncertainty, we show that voluntary measures substantially reduce the projected impact of the SARS-CoV-2 Omicron variant but that voluntary measures alone would be unlikely to completely control transmission., (© 2023. The Author(s).)

Background: Whilst other studies have reported the effectiveness of mRNA vaccination against hospitalisation, including emergency department or intensive care admission, few have assessed effectiveness against other more clinically robust indices of COVID-19 severity., Methods: A prospective single-centre test-negative design case-control study of adults hospitalised with COVID-19 disease or other acute respiratory disease between 1 June 2021 and 20 July 2022. We assessed VE (vaccine effectiveness) against hospitalisation, length of stay [LOS] >3 days, WHO COVID Score >5 and supplementary oxygen FiO 2 (fraction inspired oxygen) >28%, conducting regression analyses controlling for age, gender, index of multiple deprivation, Charlson comorbidity index, time, and community infection prevalence., Findings: 935 controls and 546 cases were hospitalised during the Delta period, with 721 controls and 372 cases hospitalised during the Omicron study period. Two-dose BNT162b2 was associated with VE 82.5% [95% confidence interval 76.2%-87.2%] against hospitalisation following Delta infection, 63.3% [26.9-81.8%], 58.5% [24.8-77.3%], and 51.5% [16.7-72.1%] against LOS >3 days, WHO COVID Score >5, and requirement for FiO2 >28% respectively. Three-dose BNT162b2 protection against hospitalisation with Omicron infection was 30.9% [5.9-49.3%], with sensitivity analyses ranging from 28.8-72.6%. Protection against LOS >3 days, WHO COVID Score >5 and requirement for FiO2 >28% was 56.1% [20.6-76.5%], 58.8% [31.2-75.8%], and 41.5% [-0.4-66.3%], respectively. In the UK, BNT162b2 was prioritised for high-risk individuals and those aged >75 years. In the latter group we found a higher estimate of VE against hospitalisation of 47.2% [16.8-66.6%]., Interpretation: BNT162b2 vaccination results in risk reductions for hospitalisation and multiple patient outcomes following Delta and Omicron COVID-19 infection, particularly in older adults. BNT162b2 remains effective against severe SARS-CoV-2 disease., Funding: AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer., Competing Interests: CH is Principal Investigator of the AvonCAP study which is an investigator-led University of Bristol study funded by 10.13039/100004319Pfizer and has previously received support from the NIHR in an Academic Clinical Fellowship. JO and LD are Co-Investigators on the AvonCAP Study. AF is a member of the Joint Committee on Vaccination and Immunization (JCVI) and chair of the World Health Organization European Technical Advisory Group of Experts on Immunization (ETAGE) committee. In addition to receiving funding from 10.13039/100004319Pfizer as Chief Investigator of this study, he leads another project investigating transmission of respiratory bacteria in families jointly funded by 10.13039/100004319Pfizer and the Gates Foundation. The other authors have no relevant conflicts of interest to declare., (© 2022 The Author(s).)

The reproduction number R has been a central metric of the COVID-19 pandemic response, published weekly by the UK government and regularly reported in the media. Here, we provide a formal definition and discuss the advantages and most common misconceptions around this quantity. We consider the intuition behind different formulations of R , the complexities in its estimation (including the unavoidable lags involved), and its value compared to other indicators (e.g. the growth rate) that can be directly observed from aggregate surveillance data and react more promptly to changes in epidemic trend. As models become more sophisticated, with age and/or spatial structure, formulating R becomes increasingly complicated and inevitably model-dependent. We present some models currently used in the UK pandemic response as examples. Ultimately, limitations in the available data streams, data quality and time constraints force pragmatic choices to be made on a quantity that is an average across time, space, social structure and settings. Effectively communicating these challenges is important but often difficult in an emergency., (© 2022 The Authors. Journal of the Royal Statistical Society: Series A (Statistics in Society) published by John Wiley & Sons Ltd on behalf of Royal Statistical Society.)

Background: The emergence of COVID-19 and public health measures implemented to reduce SARS-CoV-2 infections have both affected acute lower respiratory tract disease (aLRTD) epidemiology and incidence trends. The severity of COVID-19 and non-SARS-CoV-2 aLRTD during this period have not been compared in detail., Methods: We conducted a prospective cohort study of adults age ≥18 years admitted to either of two acute care hospitals in Bristol, UK, from August 2020 to November 2021. Patients were included if they presented with signs or symptoms of aLRTD (e.g., cough, pleurisy), or a clinical or radiological aLRTD diagnosis., Findings: 12,557 adult aLRTD hospitalisations occurred: 10,087 were associated with infection (pneumonia or non-pneumonic lower respiratory tract infection [NP-LRTI]), 2161 with no infective cause, with 306 providing a minimal surveillance dataset. Confirmed SARS-CoV-2 infection accounted for 32% (3178/10,087) of respiratory infections. Annual incidences of overall, COVID-19, and non- SARS-CoV-2 pneumonia were 714.1, 264.2, and 449.9, and NP-LRTI were 346.2, 43.8, and 302.4 per 100,000 adults, respectively. Weekly incidence trends in COVID-19 aLRTD showed large surges (median 6.5 [IQR 0.7-10.2] admissions per 100,000 adults per week), while other infective aLRTD events were more stable (median 14.3 [IQR 12.8-16.4] admissions per 100,000 adults per week) as were non-infective aLRTD events (median 4.4 [IQR 3.5-5.5] admissions per 100,000 adults per week)., Interpretation: While COVID-19 disease was a large component of total aLRTD during this pandemic period, non- SARS-CoV-2 infection still caused the majority of respiratory infection hospitalisations. COVID-19 disease showed significant temporal fluctuations in frequency, which were less apparent in non-SARS-CoV-2 infection. Despite public health interventions to reduce respiratory infection, disease incidence remains high., Funding: AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer., Competing Interests: CH is Principal Investigator of the Avon CAP study which is an investigator-led University of Bristol study funded by Pfizer and has previously received support from the NIHR in an Academic Clinical Fellowship. JO is a Co-Investigator on the Avon CAP Study. LD is further supported by UKRI through the JUNIPER consortium (grant number MR/V038613/1), MRC (grant number MC/PC/19067), EPSRC (EP/V051555/1 and The Alan Turing Institute, grant EP/N510129/1). AF is a member of the Joint Committee on Vaccination and Immunization (JCVI) and chair of the World Health Organization European Technical Advisory Group of Experts on Immunization (ETAGE) committee. In addition to receiving funding from Pfizer as Chief Investigator of this study, he leads another project investigating transmission of respiratory bacteria in families jointly funded by Pfizer and the Gates Foundation and is an investigator in trials of COVID19 vaccines including ChAdOx1nCOV-19, Janssen and Valneva vaccines. EB, JS, JC, SG, RH, SV, AV, JM, GE, and BG are employees of Pfizer and own Pfizer stock. The other authors have no relevant conflicts of interest to declare. The AvonCAP study is a University of Bristol sponsored study which is investigator-led, and funded under a collaborative agreement by Pfizer Inc., (© 2022 Published by Elsevier Ltd.)

Objectives: We aimed to evaluate the safety and optimal dose of a novel inactivated whole-virus adjuvanted vaccine against SARS-CoV-2: VLA2001., Methods: We conducted an open-label, dose-escalation study followed by a double-blind randomized trial using low, medium and high doses of VLA2001 (1:1:1). The primary safety outcome was the frequency and severity of solicited local and systemic reactions within 7 days after vaccination. The primary immunogenicity outcome was the geometric mean titre (GMT) of neutralizing antibodies against SARS-CoV-2 two weeks after the second vaccination. The study is registered as NCT04671017., Results: Between December 16, 2020, and June 3, 2021, 153 healthy adults aged 18-55 years were recruited in the UK. Overall, 81.7% of the participants reported a solicited AE, with injection site tenderness (58.2%) and headache (46.4%) being the most frequent. Only 2 participants reported a severe solicited event. Up to day 106, 131 (85.6%) participants had reported any AE. All observed incidents were transient and non-life threatening in nature. Immunogenicity measured at 2 weeks after completion of the two-dose priming schedule, showed significantly higher GMTs of SARS-CoV-2 neutralizing antibody titres in the highest dose group (GMT 545.6; 95% CI: 428.1, 695.4) which were similar to a panel of convalescent sera (GMT 526.9; 95% CI: 336.5, 825.1). Seroconversion rates of neutralizing antibodies were also significantly higher in the high-dose group (>90%) compared to the other dose groups. In the high dose group, antigen-specific IFN-γ expressing T-cells reactive against the S, M and N proteins were observed in 76, 36 and 49%, respectively., Conclusions: VLA2001 was well tolerated in all tested dose groups, and no safety signal of concern was identified. The highest dose group showed statistically significantly stronger immunogenicity with similar tolerability and safety, and was selected for phase 3 clinical development., Competing Interests: Declaration of Competing Interest AF is a member of the Joint Committee on Vaccination and immunization and chair of the WHO European Technical Advisory Group of Experts on immunization. He is an investigator or provides consultative advice on clinical trials and studies of COVID-19 vaccines produced by AstraZeneca, Janssen, Valneva, Pfizer, and Sanofi, and of other vaccines from these and other manufacturers, including GlaxoSmithKline, VPI Pharmaceuticals, Takeda, and Bionet Asia. He receives no personal remuneration or benefits for any of this work. CTA, KD, SEL, RH, IC, BQ, and JCJ are employees of Valneva Austria GmbH., (Copyright © 2022. Published by Elsevier Ltd.)

The serial interval of an infectious disease, commonly interpreted as the time between the onset of symptoms in sequentially infected individuals within a chain of transmission, is a key epidemiological quantity involved in estimating the reproduction number. The serial interval is closely related to other key quantities, including the incubation period, the generation interval (the time between sequential infections), and time delays between infection and the observations associated with monitoring an outbreak such as confirmed cases, hospital admissions, and deaths. Estimates of these quantities are often based on small data sets from early contact tracing and are subject to considerable uncertainty, which is especially true for early coronavirus disease 2019 data. In this paper, we estimate these key quantities in the context of coronavirus disease 2019 for the UK, including a meta-analysis of early estimates of the serial interval. We estimate distributions for the serial interval with a mean of 5.9 (95% CI 5.2; 6.7) and SD 4.1 (95% CI 3.8; 4.7) days (empirical distribution), the generation interval with a mean of 4.9 (95% CI 4.2; 5.5) and SD 2.0 (95% CI 0.5; 3.2) days (fitted gamma distribution), and the incubation period with a mean 5.2 (95% CI 4.9; 5.5) and SD 5.5 (95% CI 5.1; 5.9) days (fitted log-normal distribution). We quantify the impact of the uncertainty surrounding the serial interval, generation interval, incubation period, and time delays, on the subsequent estimation of the reproduction number, when pragmatic and more formal approaches are taken. These estimates place empirical bounds on the estimates of most relevant model parameters and are expected to contribute to modeling coronavirus disease 2019 transmission.

Accurate surveillance of the COVID-19 pandemic can be weakened by under-reporting of cases, particularly due to asymptomatic or pre-symptomatic infections, resulting in bias. Quantification of SARS-CoV-2 RNA in wastewater can be used to infer infection prevalence, but uncertainty in sensitivity and considerable variability has meant that accurate measurement remains elusive. Here, we use data from 45 sewage sites in England, covering 31% of the population, and estimate SARS-CoV-2 prevalence to within 1.1% of estimates from representative prevalence surveys (with 95% confidence). Using machine learning and phenomenological models, we show that differences between sampled sites, particularly the wastewater flow rate, influence prevalence estimation and require careful interpretation. We find that SARS-CoV-2 signals in wastewater appear 4-5 days earlier in comparison to clinical testing data but are coincident with prevalence surveys suggesting that wastewater surveillance can be a leading indicator for symptomatic viral infections. Surveillance for viruses in wastewater complements and strengthens clinical surveillance, with significant implications for public health., (© 2022. Crown.)

The history of the field of intersex bodies/bodies with variations of sex development (VSD) reflects the ongoing tension between sociomedical attempts to control uncertainty and reduce the duration of corporeal uncertainty by means of early diagnosis and treatment, and the embodied subjects who resist or challenge these attempts, which ultimately increase uncertainty. Based on various qualitative studies in the field of intersex, this article describes three temporal sociomedical approaches that have evolved over the last decade and aims to address the uncertainty surrounding intersex/VSD bodies. These approaches are (1) the corrective-concealing approach, which includes early surgeries and hormone therapies intended to "correct" intersex conditions and the deliberate concealment of the ambiguity and uncertainty associated with intersex conditions; (2) the preventive approach, which involves early genetic diagnostic methods aimed at regulating or preventing the recurrence of hereditary conditions under the umbrella of VSD; and (3) the wait-and-see approach, which perceives intersex bodies as natural variations and encourages parents to take time, wait, and give their children the right to bodily autonomy. A comparison of these approaches from biopolitical, phenomenological, and pragmatic perspectives reveals that time is an essential social agent in addressing and controlling uncertainty, a gatekeeper of social norms and social and physical orders, and, on the other hand, a sociopolitical agent that enables creative social change., (© 2022. Springer Nature Switzerland AG.)

Objetivo. Estimar la seroprevalencia de SARS-CoV-2 en población de edad escolar en México. Material y métodos. Se categorizaron a niños y adolescentes que participaron en la Encuesta Nacional de Salud y Nutrición 2020 sobre Covid-19 (Ensanut 2020 Covid-19) por edad escolar y nivel educativo. En participantes seropositivos, se identificó la proporción de infecciones asintomáticas. Se estimaron razones de prevalencia usando un modelo de regresión log-binomial. Resultados. La seroprevalencia en educación básica y media fue de 18.7% (IC95%: 14.9, 22.5) y 26.7% (IC95%: 22.1, 31.3), respectivamente. La infección asintomática fue más frecuente en educación básica (88.5% [IC95%: 80.5, 93.5]). Conclusiones. En población de educación básica la infección por SARS-CoV-2 es baja y usualmente asintomática.

Background: On Dec 8, 2020, deployment of the first SARS-CoV-2 vaccination authorised for UK use (BNT162b2 mRNA vaccine) began, followed by an adenoviral vector vaccine ChAdOx1 nCoV-19 on Jan 4, 2021. Care home residents and staff, frontline health-care workers, and adults aged 80 years and older were vaccinated first. However, few data exist regarding the effectiveness of these vaccines in older people with many comorbidities. In this post-implementation evaluation of two COVID-19 vaccines, we aimed to determine the effectiveness of one dose in reducing COVID-19-related admissions to hospital in people of advanced age., Methods: This prospective test-negative case-control study included adults aged at least 80 years who were admitted to hospital in two NHS trusts in Bristol, UK with signs and symptoms of respiratory disease. Patients who developed symptoms before receiving their vaccine or those who received their vaccine after admission to hospital were excluded, as were those with symptoms that started more than 10 days before hospital admission. We did logistic regression analysis, controlling for time (week), sex, index of multiple deprivations, and care residency status, and sensitivity analyses matched for time and sex using a conditional logistic model adjusting for index of multiple deprivations and care residency status. This study is registered with ISRCTN, number 39557., Findings: Between Dec 18, 2020, and Feb 26, 2021, 466 adults were eligible (144 test-positive and 322 test-negative). 18 (13%) of 135 people with SARS-CoV-2 infection and 90 (34%) of 269 controls received one dose of BNT162b2. The adjusted vaccine effectiveness was 71·4% (95% CI 46·5-90·6). Nine (25%) of 36 people with COVID-19 infection and 53 (59%) of 90 controls received one dose of ChAdOx1 nCoV-19. The adjusted vaccine effectiveness was 80·4% (95% CI 36·4-94·5). When BNT162b2 effectiveness analysis was restricted to the period covered by ChAdOx1 nCoV-19, the estimate was 79·3% (95% CI 47·0-92·5)., Interpretation: One dose of either BNT162b2 or ChAdOx1 nCoV-19 resulted in substantial risk reductions of COVID-19-related hospitalisation in people aged at least 80 years., Funding: Pfizer., Competing Interests: Declaration of interests CH is principal investigator of the Avon CAP study which is an investigator-led University of Bristol study funded by Pfizer and has previously received support from the NIHR in an academic clinical fellowship. JO is a co-investigator on the Avon CAP study. LD is further supported by UKRI through the JUNIPER consortium (grant number MR/V038613/1), MRC (grant number MC/PC/19067), EPSRC (EP/V051555/1 and The Alan Turing Institute, grant EP/N510129/1). AF is a member of the JCVI and is chair of WHO's European Technical Advisory Group of Experts on Immunization committee. In addition to receiving funding from Pfizer as chief investigator of this study, he leads another project investigating transmission of respiratory bacteria in families jointly funded by Pfizer and the Gates Foundation and is an investigator in trials of COVID-19 vaccines including ChAdOx1 nCOV-19, Janssen, and Valneva vaccines. The other authors have no relevant conflicts of interest to declare., (Copyright © 2021 Elsevier Ltd. All rights reserved.)