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COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose in June 2021. Monovalent messenger RNA (mRNA) COVID-19 vaccines were subsequently widely used for the third and fourth-dose vaccination campaigns in high-income countries. Real-world vaccine effectiveness against symptomatic infections following third doses declined during the Omicron wave. This report compares the immunogenicity and kinetics of responses to third doses of vaccines from day (D) 28 to D242 following third doses in seven study arms. The trial initially included ten experimental vaccine arms (seven full-dose, three half-dose) delivered at three groups of six sites. Participants in each site group were randomised to three or four experimental vaccines, or MenACWY control. The trial was stratified such that half of participants had previously received two primary doses of ChAdOx1 nCov-19 (Oxford–AstraZeneca; hereafter referred to as ChAd) and half had received two doses of BNT162b2 (Pfizer–BioNtech, hereafter referred to as BNT). The D242 follow-up was done in seven arms (five full-dose, two half-dose). The BNT vaccine was used as the reference as it was the most commonly deployed third-dose vaccine in clinical practice in high-income countries. The primary analysis was conducted using all randomised and baseline seronegative participants who were SARS-CoV-2 naïve during the study and who had not received a further COVID-19 vaccine for any reason since third dose randomisation. Among the 817 participants included in this report, the median age was 72 years (IQR: 55–78) with 50.7% being female. The decay rates of anti-spike IgG between vaccines are different among both populations who received initial doses of ChAd/ChAd and BNT/BNT. In the population that previously received ChAd/ChAd, mRNA vaccines had the highest titre at D242 following their vaccine dose although Ad26. COV2. S (Janssen; hereafter referred to as Ad26) showed slower decay. For people who received BNT/BNT as their initial doses, a slower decay was also seen in the Ad26 and ChAd arms. The anti-spike IgG became significantly higher in the Ad26 arm compared to the BNT arm as early as 3 months following vaccination. Similar decay rates were seen between BNT and half-BNT; the geometric mean ratios ranged from 0.76 to 0.94 at different time points. The difference in decay rates between vaccines was similar for wild-type live virus-neutralising antibodies and that seen for anti-spike IgG. For cellular responses, the persistence was similar between study arms. Heterologous third doses with viral vector vaccines following two doses of mRNA achieve more durable humoral responses compared with three doses of mRNA vaccines. Lower doses of mRNA vaccines could be considered for future booster campaigns. • Humoral responses following booster doses of adenoviral vector vaccines decay slower than following booster doses of mRNA vaccines. • Lower doses of mRNA vaccines as boosters may be equally as effective. • Further investigation into heterologous vaccine schedules for COVID-19 is warranted. [ABSTRACT FROM AUTHOR]

Heterologous COVID vaccine priming schedules are immunogenic and effective. This report aims to understand the persistence of immune response to the viral vectored, mRNA and protein-based COVID-19 vaccine platforms used in homologous and heterologous priming combinations, which will inform the choice of vaccine platform in future vaccine development. Com-COV2 was a single-blinded trial in which adults ≥ 50 years, previously immunised with single dose 'ChAd' (ChAdOx1 nCoV-19, AZD1222, Vaxzevria, Astrazeneca) or 'BNT' (BNT162b2, tozinameran, Comirnaty, Pfizer/BioNTech), were randomised 1:1:1 to receive a second dose 8–12 weeks later with either the homologous vaccine, or 'Mod' (mRNA-1273, Spikevax, Moderna) or 'NVX' (NVX-CoV2373, Nuvaxovid, Novavax). Immunological follow-up and the secondary objective of safety monitoring were performed over nine months. Analyses of antibody and cellular assays were performed on an intention-to-treat population without evidence of COVID-19 infection at baseline or for the trial duration. In April/May 2021, 1072 participants were enrolled at a median of 9.4 weeks after receipt of a single dose of ChAd (N = 540, 45% female) or BNT (N = 532, 39% female) as part of the national vaccination programme. In ChAd-primed participants, ChAd/Mod had the highest anti-spike IgG from day 28 through to 6 months, although the heterologous vs homologous geometric mean ratio (GMR) dropped from 9.7 (95% CI (confidence interval): 8.2, 11.5) at D28 to 6.2 (95% CI: 5.0, 7.7) at D196. The heterologous/homologous GMR for ChAd/NVX similarly dropped from 3.0 (95% CI:2.5,3.5) to 2.4 (95% CI:1.9, 3.0). In BNT-primed participants, decay was similar between heterologous and homologous schedules with BNT/Mod inducing the highest anti-spike IgG for the duration of follow-up. The adjusted GMR (aGMR) for BNT/Mod compared with BNT/BNT increased from 1.36 (95% CI: 1.17, 1.58) at D28 to 1.52 (95% CI: 1.21, 1.90) at D196, whilst for BNT/NVX this aGMR was 0.55 (95% CI: 0.47, 0.64) at day 28 and 0.62 (95% CI: 0.49, 0.78) at day 196. Heterologous ChAd-primed schedules produced and maintained the largest T-cell responses until D196. Immunisation with BNT/NVX generated a qualitatively different antibody response to BNT/BNT, with the total IgG significantly lower than BNT/BNT during all follow-up time points, but similar levels of neutralising antibodies. Heterologous ChAd-primed schedules remain more immunogenic over time in comparison to ChAd/ChAd. BNT-primed schedules with a second dose of either mRNA vaccine also remain more immunogenic over time in comparison to BNT/NVX. The emerging data on mixed schedules using the novel vaccine platforms deployed in the COVID-19 pandemic, suggest that heterologous priming schedules might be considered as a viable option sooner in future pandemics. ISRCTN:27841311 EudraCT:2021-001275-16. • Heterologous versus homologous AZ-primed schedules retain higher antibodies over time. • Priming schedules with two mRNA vaccine doses remain the most humorally immunogenic. • Neutralising antibody response is proportionally greater in Pfizer/Novavax. • Novavax-boosted regimens are less immunogenic in participants with greater BMI. • Heterologous priming schedules should be considered sooner in future pandemics. [ABSTRACT FROM AUTHOR]

Bloodstream infection or sepsis is a common cause of mortality globally. Staphylococcus aureus (S. aureus) is of particular concern, through its ability to seed metastatic infections in almost any organ after entering the bloodstream (S. aureus bacteraemia), often without localising signs. A positive blood culture for S. aureus bacteria should lead to immediate and urgent identification of the cause. Failure to detect a precise focus of infection is associated with higher mortality, sometimes despite appropriate antibiotics. This is likely due to the limited ability to effectively target therapy in occult lesions. Early detection of foci of metastatic S. aureus infection is therefore key for optimal diagnosis and subsequent therapeutic management. 18F-FDG-PET/CT and MRI offer us invaluable tools in the localisation of foci of S. aureus infection. Crucially, they may identify unexpected foci at previously unsuspected locations in the body, for example vertebral osteomyelitis in the absence of back pain. S. aureus bloodstream infections are further complicated by their microbiological recurrence; 18F-FDG-PET/CT provide a means of localising, thus enabling source control. More evidence is emerging as to the utility of 18F-FDG-PET/CT in this setting, perhaps even to the point of reducing mortality. 18 F-FDG-PET/MRI may have a similar impact. The available evidence demonstrates a need to investigate the impact of 18F-FDG-PET/CT and MRI scanning in clinical management and outcomes of S. aureus infection further in a randomised prospective clinical trial. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the persistence of immunogenicity three months after third dose boosters.Methods: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study.Results: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30-94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461-10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 μg) or BNT (30 μg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 μg) versus BNT (30 μg) ranging between 0.74-0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses.Conclusions: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses. [ABSTRACT FROM AUTHOR]

Cycling injury risk is an important topic, but few studies explore cycling risk in relation to exposure. This is largely because of a lack of exposure data, in other words how much cycling is done at different locations. This paper helps to fill this gap. It reports a case-control study of cycling injuries in London in 2013–2014, using modelled cyclist flow data alongside datasets covering some characteristics of the London route network. A multilevel binary logistic regression model is used to investigate factors associated with injury risk, comparing injury sites with control sites selected using the modelled flow data. Findings provide support for ‘safety in numbers’: for each increase of a natural logarithmic unit (2.71828) in cycling flows, an 18% decrease in injury odds was found. Conversely, increased motor traffic volume is associated with higher odds of cycling injury, with one logarithmic unit increase associated with a 31% increase in injury odds. Twenty-mile per hour compared with 30mph speed limits were associated with 21% lower injury odds. Residential streets were associated with reduced injury odds, and junctions with substantially higher injury odds. Bus lanes do not affect injury odds once other factors are controlled for. These data suggest that speed limits of 20 mph may reduce cycling injury risk, as may motor traffic reduction. Further, building cycle routes that generate new cycle trips should generate ‘safety in numbers’ benefits. [ABSTRACT FROM AUTHOR]

This paper analyses Active People Survey data (collected 2011/12 to 2015/16) on 789,196 English adults, providing new information on how a range of socio-demographic factors are associated with utility and leisure cycling. Substantial inequalities are found in relation to gender, age, disability, and ethnicity for both types of cycling. For gender and age, and perhaps for disability in relation to recreational cycling, inequalities are moderated by local cycling prevalence such that English authorities with more cycling see less inequality. For education and car ownership, the picture is more mixed. Individuals with higher educational levels are more likely to participate in leisure cycling, but within most English local authorities this association is absent for utility cycling. Car ownership is negatively associated with utility cycling, but positively associated with recreational cycling. The paper’s discussion section puts these inequalities in context, and discusses the significance of the fact that some inequalities seem to be less pronounced or even absent in some contexts. It is argued that more research and a broader conceptualisation of cycling inequalities are needed to better understand and address inequalities in cycling participation. [ABSTRACT FROM AUTHOR]

Using 2014 and 2015 data from the UK Near Miss Project, this paper examines the stability of self-report incident rates for cycling near misses across these two years. It further examines the stability of the individual-level predictors of experiencing a near miss, including what influences the scariness of an incident. The paper uses three questions asked for only in 2015, which allow further exploration of factors shaping near miss rates and impacts of incidents. Firstly, a respondent's level of cycling experience; secondly, whether an incident was perceived as deliberate; and finally, whether the respondent themselves described the incident as a ‘near miss' (as opposed to only a frightening and/or annoying non-injury incident). Using this data, we find a decline of almost a third in incident rates in 2015 compared to 2014, which we believe is likely to be largely an artefact due to differences in reporting rates. This suggests caution about interpreting small fluctuations in subjectively reported near miss rates. However, in both years near miss rates are many times more frequent than injury collisions. In both years of data collection our findings are very similar in terms of the patterning of incident types, and how frightening different incident categories are, which increases confidence in these findings. We find that new cyclists experience very high incident rates compared to other cyclists, and test a conceptual model explaining how perceived deliberateness, near-miss status, and scariness are connected. For example, incidents that are perceived to be deliberate are more likely to be experienced as very frightening, independent of their ‘near miss’ status. [ABSTRACT FROM AUTHOR]

The article discusses a study on dementia and its possible predictors focusing on childhood school performance, educational attainment, and occupational complexity with data, people, and things. Topics covered include the influence of brain and cognitive reserve in dementia neuropathology, the extraneous variables implemented such as sex, birth, and year of follow-up by the researchers, and the protective effects of higher school grades and complex occupational roles.

Cycling confers transport, health and environmental benefits, and bicycle sharing systems are an increasingly popular means of promoting urban cycling. Following the launch of the London bicycle sharing system (LBSS) in 2010, women and residents of deprived areas were under-represented among initial users. This paper examines how the profile of users has changed across the scheme’s first 3 years, using total-population registration and usage data. We find that women still make fewer than 20% of all ‘registered-use’ LBSS trips, although evidence from elsewhere suggests that the introduction of ‘casual’ use has encouraged a higher overall female share of trips. The proportion of trips by registered users from ‘highly-deprived areas’ (in the top tenth nationally for income deprivation) rose from 6% to 12%. This was due not only to the 2012 LBSS extension to some of London’s poorest areas, but also to a steadily increasing share of trips by residents of highly-deprived areas in the original LBSS zone. Indirect evidence suggests, however, that the twofold increase in LBSS prices in January 2013 has disproportionately discouraged casual-use trips among residents of poorer areas. We conclude that residents in deprived areas can and do use bicycle sharing systems if these are built in their local areas, and may do so progressively more over time, but only if the schemes remain affordable relative to other modes. [ABSTRACT FROM AUTHOR]

Highlights: [•] The first controlled, longitudinal cohort study evaluating effects of new walking and cycling routes on CO2 emissions. [•] We found no significant change in transport CO2 emissions despite the new routes being well used by walkers and cyclists. [•] We found no significant change in transport CO2 emissions despite increases in active travel and physical activity. [•] A more comprehensive approach to active travel promotion may be needed to achieve transport CO2 savings. [ABSTRACT FROM AUTHOR]

Cycling confers health and environmental benefits, but few robust studies have evaluated large-scale programmes to promote cycling. In England, recent years have seen substantial, town-wide cycling initiatives in six Cycling Demonstration Towns (funded 2005–2011) and 12 Cycling Cities and Towns (funded 2008–2011). The initiatives involved mixtures of capital investment (e.g. cycle lanes) and revenue investment (e.g. cycle training), tailored to each town. This controlled before-after natural experimental study used English census data to examine impacts on the prevalence of travelling to work by bicycle and other modes, comparing changes in the intervention towns with changes in three comparison groups (matched towns, unfunded towns and a national comparison group). We also compared effects between more and less deprived areas, and used random-effects meta-analysis to compare intervention effects between towns. Among 1.3 million commuters in 18 intervention towns, we found that the prevalence of cycling to work rose from 5.8% in 2001 to 6.8% in 2011. This represented a significant increase relative to all three comparison groups (e.g. +0.69 (95% CI 0.60,0.77) percentage points for intervention vs. matched towns). Walking to work also increased significantly compared with comparison towns, while driving to work decreased and public transport use was unchanged. These effects were observed across all fifths of area deprivation, with larger relative changes in deprived areas. There was substantial variation in effect sizes between towns, however, and the average town-level effect on cycling was non-significant (+0.29 (−0.26,0.84) percentage points for intervention vs. matched towns). We conclude that to date, cycling to work has increased (and driving to work decreased) in the intervention towns, in a relatively equitable manner. The variation in effects between towns indicates uncertainty regarding the likely impact of comparable investment in future towns. Nevertheless these results support the case for implementing and evaluating further town-wide cycling initiatives. [Copyright &y& Elsevier]

Abstract: Access to transport is an important determinant of health, and concessionary fares for public transport are one way to reduce the ‘transport exclusion’ that can limit access. This paper draws on qualitative data from two groups typically at risk of transport exclusion: young people (12–18 years of age, n = 118) and older citizens (60+ years of age, n = 46). The data were collected in London, UK, where young people and older citizens are currently entitled to concessionary bus travel. We focus on how this entitlement is understood and enacted, and how different sources of entitlement mediate the relationship between transport and wellbeing. Both groups felt that their formal entitlement to travel for free reflected their social worth and was, particularly for older citizens, relatively unproblematic. The provision of a concessionary transport entitlement also helped to combat feelings of social exclusion by enhancing recipients' sense of belonging to the city and to a ‘community’. However, informal entitlements to particular spaces on the bus reflected less valued social attributes such as need or frailty. Thus in the course of travelling by bus the enactment of entitlements to space and seats entailed the negotiation of social differences and personal vulnerabilities, and this carried with it potential threats to wellbeing. We conclude that the process, as well as the substance, of entitlement can mediate wellbeing; and that where the basis for providing a given entitlement is widely understood and accepted, the risks to wellbeing associated with enacting that entitlement will be reduced. [Copyright &y& Elsevier]

Abstract: Carbon dioxide (CO2) emissions from motorised travel are hypothesised to be associated with individual, household, spatial and other environmental factors. Little robust evidence exists on who contributes most (and least) to travel CO2 and, in particular, the factors influencing commuting, business, shopping and social travel CO2. This paper examines whether and how demographic, socio-economic and other personal and environmental characteristics are associated with land-based passenger transport and associated CO2 emissions. Primary data were collected from 3474 adults using a newly developed survey instrument in the iConnect study in the UK. The participants reported their past-week travel activity and vehicle characteristics from which CO2 emissions were derived using an adapted travel emissions profiling method. Multivariable linear and logistic regression analyses were used to examine what characteristics predicted higher CO2 emissions. CO2 emissions from motorised travel were distributed highly unequally, with the top fifth of participants producing more than two fifth of emissions. Car travel dominated overall CO2 emissions, making up 90% of the total. The strongest independent predictors of CO2 emissions were owning at least one car, being in full-time employment and having a home-work distance of more than 10km. Income, education and tenure were also strong univariable predictors of CO2 emissions, but seemed to be further back on the causal pathway than having a car. Male gender, late-middle age, living in a rural area and having access to a bicycle also showed significant but weaker associations with emissions production. The findings may help inform the development of climate change mitigation policies for the transport sector. Targeting individuals and households with high car ownership, focussing on providing viable alternatives to commuting by car, and supporting planning and other policies that reduce commuting distances may provide an equitable and efficient approach to meeting carbon mitigation targets. [Copyright &y& Elsevier]

Abstract: Encouraging people out of their cars and into other modes of transport, which has major advantages for health, the environment and urban development, has proved difficult. Greater understanding of the influences that lead people to use the car, particularly for shorter journeys, may help to achieve this. This paper examines the predictors of car use compared with the bicycle to explore how it may be possible to persuade more people to use the bicycle instead of the car. Multivariable logistic regression was used to examine the socio-demographic, transport and health-related correlates of mode choice for work, shopping and leisure trips in Cambridge, a city with high levels of cycling by UK standards. The key findings are that commuting distance and free workplace parking were strongly associated with use of the car for work trips, and car availability and lower levels of education were associated with car use for leisure, shopping and short-distanced commuting trips. The case of Cambridge shows that more policies could be adopted, particularly a reduction in free car parking, to increase cycling and reduce the use of the car, especially over short distances. [Copyright &y& Elsevier]

Abstract: Car use is associated with substantial health and environmental costs but research in deprived populations indicates that car access may also promote psychosocial well-being within car-oriented environments. This mixed-method (quantitative and qualitative) study examined this issue in a more affluent setting, investigating the socio-economic structure of car commuting in Cambridge, UK. Our analyses involved integrating self-reported questionnaire data from 1142 participants in the Commuting and Health in Cambridge study (collected in 2009) and in-depth interviews with 50 participants (collected 2009–2010). Even in Britain''s leading ‘cycling city’, cars were a key resource in bridging the gap between individuals'' desires and their circumstances. This applied both to long-term life goals such as home ownership and to shorter-term challenges such as illness. Yet car commuting was also subject to constraints, with rush hour traffic pushing drivers to start work earlier and with restrictions on, or charges for, workplace parking pushing drivers towards multimodal journeys (e.g. driving to a ‘park-and-ride’ site then walking). These patterns of car commuting were socio-economically structured in several ways. First, the gradient of housing costs made living near Cambridge more expensive, affecting who could ‘afford’ to cycle and perhaps making cycling the more salient local marker of Bourdieu''s class distinction. Nevertheless, cars were generally affordable in this relatively affluent, highly-educated population, reducing the barrier which distance posed to labour-force participation. Finally, having the option of starting work early required flexible hours, a form of job control which in Britain is more common among higher occupational classes. Following a social model of disability, we conclude that socio-economic advantage can make car-oriented environments less disabling via both greater affluence and greater job control, and in ways manifested across the full socio-economic range. This suggests the importance of combining individual-level ‘healthy travel’ interventions with measures aimed at creating travel environments in which all social groups can pursue healthy and satisfying lives. [Copyright &y& Elsevier]

The article presents a research study concerning the impacts of childhood adversities on the mental health outcomes of students in Kabul, Afghanistan. It notes that the findings of the study reveal that the major contributing factor to depression is conflict within the family. Meanwhile, this study was developed in an attempt to determine possible interventions to effectively modify these negative outcomes.

Abstract: This study examines traffic-related air pollution in London in relation to area- and individual-level socio-economic position (SEP). Mean air pollution concentrations were generally higher in postcodes of low SEP as classified by small-area markers of deprivation (Index of Multiple Deprivation (IMD) domains) and by the postcode-level ACORN geodemographic marker. There were exceptions, however, including reversed directions of associations in central London and for SEP markers relating to education. ACORN predicted air pollution independently of IMD and explained additional variation at the postcode level, indicating the potential value of using both markers in air pollution epidemiology studies. By contrast, after including IMD and ACORN there remained little relationship between air pollution and individual-level SEP or smoking, suggesting limited residual socio-economic confounding in epidemiological studies with comprehensive area-level adjustment. [Copyright &y& Elsevier]

Abstract: Humans are an exceptionally intelligent species, and the selective pressures which may have shaped these advanced cognitive powers are therefore of interest. This study investigates the fitness consequences of pre-reproductive school performance in a Swedish population-based cohort of 5244 males and 4863 females born 1915-1929. School performance was measured at around age 10 using three variables: mean school marks, being promoted/held back in school, and recognised learning difficulties. Our primary outcomes were probability of ever marrying, total number of children and total number of grandchildren. In males (but not females), poorer school performance predicted fewer children and grandchildren. This was primarily mediated via probability of marriage; mortality and fertility within marriage were not important mediating pathways. The effect of school performance upon marriage in males was independent of early-life social and biological characteristics, including birth weight for gestational age, preterm birth, family composition, and family socioeconomic position. The effect of school performance upon the probability of marriage in males was, however, largely mediated by adult socioeconomic position. This suggests that in general sexual selection for cognitive abilities per se did not play a major role in either males or females in this cohort. Adult socioeconomic position did not, however, fully explain the marriage disadvantage in males or (at marginal significance) females with particularly poor school performance. We conclude that school performance can affect long-term reproductive success. In this population, however, the effect is confined to males and is largely mediated by the increased probability of marriage which comes with their greater socioeconomic success. [Copyright &y& Elsevier]

Abstract: Studying biological and social determinants of mortality and fertility provides insight into selective pressures in a population and the possibility of trade-offs between short- and long-term reproductive success. Limited data is available from post-demographic transition populations. We studied determinants of reproductive success using multi-generational data from a large, population-based cohort of 13,666 individuals born in Sweden between 1915 and 1929. We studied the effects of birthweight for gestational age, preterm birth, birth multiplicity, birth order, mother''s age, mother''s marital status and family socioeconomic position (SEP) upon reproductive success, measured as total number of children and grandchildren. We further tested the hypothesis that number of grandchildren would peak at intermediate family size, as predicted by some life history explanations for fertility limitation. Reproductive success was associated with both social and biological characteristics at birth. In both sexes, a higher birthweight for gestational age, a term birth and a younger mother were independently associated with a greater number of descendants. A married mother and higher family SEP were also associated with a greater number of descendants in males (but not in females), while higher birth order was associated with a greater number of descendents in females (but not males). These effects were mediated by sex-specific effects upon the probability of marriage. Marriage was also affected by other early life characteristics including birthweight, indicating how ‘biological’ characteristics may operate via social pathways. Number of grandchildren increased with increasing number of children in both sexes, providing no evidence for a trade-off between quantity of offspring and their subsequent reproductive ‘quality’. [Copyright &y& Elsevier]

The article evaluates the dimensionality of the total difficulties score of the Strengths and Difficulties Questionnaire (SDQ) which is a widely used measure of child mental health. To do so, researchers are validating the SDQ across its full range against the prevalence of clinical disorder. It was found that children with higher total difficulty scores have greater psychopathology as judged by the prevalence of clinical disorder across the full range of the parent, teacher and youth SDQ. The odds of disorder increases at a constant rate across the range.

Patients with some types of immunodeficiency can experience chronic or relapsing infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This leads to morbidity and mortality, infection control challenges, and the risk of evolution of novel viral variants. The optimal treatment for chronic coronavirus disease 2019 (COVID-19) is unknown. Our aim was to characterize a cohort of patients with chronic or relapsing COVID-19 disease and record treatment response. We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features, and treatment response of immunodeficient patients with chronic (lasting ≥21 days) or relapsing (≥2 episodes) of COVID-19. We identified 31 patients (median age 49 years). Their underlying immunodeficiency was most commonly characterized by antibody deficiency with absent or profoundly reduced peripheral B-cell levels; prior anti-CD20 therapy, and X-linked agammaglobulinemia. Their clinical features of COVID-19 were similar to those of the general population, but their median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to 5 episodes of illness. Remdesivir monotherapy (including when given for prolonged courses of ≤20 days) was associated with sustained viral clearance in 7 of 23 clinical episodes (30.4%), whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 mAbs resulted in viral clearance in 13 of 14 episodes (92.8%). Patients receiving no therapy did not clear SARS-CoV-2. COVID-19 can present as a chronic or relapsing disease in patients with antibody deficiency. Remdesivir monotherapy is frequently associated with treatment failure, but the combination of remdesivir with antibody-based therapeutics holds promise. [ABSTRACT FROM AUTHOR]

Abstract: While Huntington''s disease (HD) is a condition that primarily involves the basal ganglia, there is evidence to suggest that the hypothalamus is also affected. Because the osmoreceptors regulating thirst are situated in the circumventricular region of the hypothalamus, we were interested in whether altered thirst is a part of the HD phenotype. We used the LABORAS behavioural monitoring system and water consumption to show that drinking behaviour was abnormal in R6/2 mice. By 10 weeks of age, R6/2 mice spent significantly more time drinking and drank a greater volume than their wild-type (WT) littermates. The numbers of immunoreactive vasopressin neurons in the paraventricular nucleus (PVN) of the hypothalamus in R6/2 mice were significantly decreased from 8 weeks of age, suggesting that the change in drinking behaviour may be the result of hypothalamic dysfunction. We gave a xerostomia (dry mouth) questionnaire to HD patients and control subjects, and also measured their urine osmolality and serum vasopressin. The mean total xerostomia score was significantly higher in HD patients than in controls, indicating greater thirst in HD patients. Urine osmolality was unaffected in HD patients up to clinical stage III, and none of the patients had diabetes. However, serum vasopressin was increased, suggesting a dysregulation in the control of hypothalamic vasopressin release. A dry mouth can affect taste, mastication and swallowing, all of which may contribute to the significant weight loss seen in both HD patients and R6/2 mice, as can dehydration. We suggest that increased thirst may be an important and clinically relevant biomarker for the study of disease progression in HD. [Copyright &y& Elsevier]

Summary: We report the first case of a hamartoma, arising from peripheral lung tissue, which extended proximally over several decades to occlude the large airways. The patient''s symptoms were originally attributed to asthma and the correct diagnosis was only made when she developed life-threatening airway obstruction. The endobronchial component of the hamartoma was debulked with urgent laser therapy, while the peripheral base of the tumour was resected by elective right middle lobectomy. [Copyright &y& Elsevier]

Objective: To identify risk factors for poor child mental health in the southeastern Brazilian municipality of Taubaté.Method: In 2001 we carried out a representative school-based survey of Brazilian schoolchildren ages 7 to 14 years (response rate, 83%). We collected extensive data on child mental health and on potential risk and protective factors at baseline (N = 1,112) and collected follow-up information on mental health outcome after 3 years (N = 760). We used the Strengths and Difficulties Questionnaire as a dimensional measure of mental health at both time points and the Development and Well-Being Assessment to diagnose psychiatric disorder at baseline.Results: Cross-sectionally, both dimensional and diagnostic measures of child psychopathology were associated with dangerous area, nontraditional family, parental stress, harsh physical punishment, poor general health, low IQ, repeating a year at school, and male gender. There were different cross-sectional associations with different types of psychopathology. Psychological difficulties were moderately persistent across time. Younger age, lower maternal education, and lower child's IQ predicted a worse prognosis even after adjusting for initial psychopathology.Conclusions: The multiple factors associated with Brazilian child mental health are broadly in line with previous findings elsewhere. Public health programs to foster child mental health need multiple targets, but may benefit a wide range of the population. [ABSTRACT FROM AUTHOR]

Summary: Talc pleurodesis is commonly used in the palliative treatment of malignant pleural effusions but the shortest and most effective regime has not been determined. In particular, it is not clear when the intercostal drain should be removed following the insertion of sclerosant. We conducted a single-centre, randomised, open trial of drain removal at 24h versus 72h following talc slurry pleurodesis. The primary outcome measure was success of pleurodesis (no recurrence of effusion on chest radiograph at 1-month follow-up) and secondary outcome measures included length of hospital stay and mortality. We found no difference between recurrence of pleural effusion in those randomised to drain removal at 24h and those randomised to drain removal at 72h (p >0.5). However, length of stay was significantly reduced when the chest drain was removed at 24h (4 days versus 8 days; p <0.01). Mortality did not differ between the two groups. We conclude that this shorter pleurodesis regime is safe and effective. [Copyright &y& Elsevier]

A response from the authors of the article "A life-course study of cognitive reserve in dementia: From childhood to old age," which was published in a previous issue is presented.

A letter to the editor is presented in response to the article "A life-course study of cognitive reserve in dementia: From childhood to old age," by Serhiy Dekhtyar, Kirk Scott, Hiu-Xin Wang, and others, along with a response from the authors, is presented.

• Main roads, downhill gradients, and wider roads carry higher injury risk for people cycling. • High streets are associated with increased risk of injury. • Bus lanes, guard railing, parking lots, and parked cars all raise injury risk. • Typical British cycle infrastructure fails to protect cyclists, with paint-based lanes raising risk. • Policy recommendations include removing guard railing and building better cycle infrastructure. This paper examines infrastructural and route environment correlates of cycling injury risk in Britain. We used a case-crossover design, randomly selecting control sites from modelled cyclist routes, comparing these with sites where cyclists were injured. We then used conditional logistic regression for matched case–control groups modelling to compare characteristics of control and injury sites. Intersections were strongly associated with injury risk. High streets were associated with an elevated injury risk in final adjusted models, as was road type being primary, and a more downhill gradient. Lower speed limits and lower motor traffic connectivity were initially associated with lower injury risk, but these effects were no longer statistically significant in adjusted models. Increased road width was associated with increased injury risk in all models. Increased injury risk was associated in all models with presence of bus lane (somewhat mitigated at stops), guardrail, and fuel station or parking lot. Presence of parked cars in street view data raised injury risk in fully adjusted models, as did congestion (measured by low morning peak speeds), while higher volumes of people cycling along the street reduced it. In fully adjusted models, a statistically significant increase in risk was associated with presence of an on-road painted cycle lane. Most cycle lanes or tracks at control and injury sites were very poor, with narrow lanes, shared footways, and lack of protection at junctions. Given findings from other studies showing protective effects of cycle infrastructure, Britain must create higher quality cycle provision, avoiding narrow on-road painted lanes. [ABSTRACT FROM AUTHOR]

• Paper reports one-year findings from a longitudinal study of London 'mini-Hollands'. • Interventions were associated with increased likelihood of any past-week cycling. • Interventions were associated with increased past-week active travel time. • They were associated with perceived improvements to cycling and street environments. • No evidence either way of change in car use associated with interventions. More evidence is needed on the impacts of building infrastructure for walking and cycling. A knowledge gap and an implementation gap have been mutually reinforcing. This paper reports on a longitudinal study examining the impacts of the still in progress 'mini-Hollands programme', which seeks to transform local environments for walking and cycling, in three Outer London boroughs. Compared to Inner London, Outer London has low levels of cycling and low levels of walking, and is relatively car dependent. We conducted a longitudinal study of 1712 individuals sampled from households in mini-Holland boroughs (intervention sample) and from non mini-Holland Outer London boroughs (control sample). The intervention sample was further divided, a priori, into those living in "high-dose neighbourhoods", where substantial changes to the local walking and cycling infrastructure had been implemented, versus "low-dose neighbourhoods" where such improvements had not (yet) been made. At both baseline (2016) and one-year follow-up (2017), we administered an online survey of travel behaviour and attitudes to transport and the local environment. One year's worth of interventions was associated with an increase in active travel among those living in areas defined as 'high-dose' neighbourhoods. Specifically, those in high-dose areas were 24% more likely to have done any past-week cycling at follow-up, compared to those living in non mini-Holland areas (95% CI, 2% to 52%). The mid-point estimate for increase in active travel (walking plus cycling) time for the same group was an additional 41.0 min (95% CI 7.0, 75.0 min). Positive changes in views about local environments were recorded in intervention areas, driven by a perceived improvement in cycling-related items. Controversy related to the interventions is expressed in a growth in perceptions that 'too much' money is spent on cycling in intervention areas. However, intervention areas also saw a reduction in perceptions that 'too little' money is spent (the latter view being common both at baseline and Wave 1 in control areas). Overall, the findings here suggest that programme interventions, while controversial, are having a measurable and early impact on active travel behaviour and perceptions of the local cycling environment. [ABSTRACT FROM AUTHOR]

Background São Paulo city, Brazil, faces challenges caused by rapid urbanization. We illustrate how future travel patterns could lead to different health consequences in the city. Methods We evaluated the health impacts of different travel pattern scenarios for the São Paulo adult population by comparing the travel patterns of São Paulo in 2012 with counterfactual scenarios in which the city adopted travel patterns of i) those living in the city's expanded centre; ii) London (2012); iii) a highly motorized São Paulo (SP California); and iv) a visionary São Paulo (SP 2040), with high levels of walking and cycling and low levels of car and motorcycle use. For each scenario we estimated changes in exposure to air pollution, road injury risk, and physical activity. Health outcomes were estimated using disability adjusted life years (DALYs) and premature deaths averted. Sensitivity analyses were performed to identify the main sources of uncertainty. Results We found considerable health gains in the SP 2040 scenario (total 63.6 k DALYs avoided), with 4.7% of premature deaths from ischemic heart disease avoided from increases in physical activity alone. Conversely, we found substantial health losses in the scenario favouring private transport (SP California, total increase of 54.9 k DALYs), with an increase in road traffic deaths and injuries among pedestrians and motorized vehicles. Parameters related to air pollution had the largest impact on uncertainty. Conclusions Shifting travel patterns towards more sustainable transport can provide major health benefits in São Paulo. Reducing the uncertainties in the findings should be a priority for empirical and modelling research on the health impacts of such shifts. [ABSTRACT FROM AUTHOR]

Anti–SARS-CoV-2 vaccination has saved millions of lives in the past few years. To maintain a high level of protection, particularly in at-risk populations, booster doses are recommended to counter the waning of circulating antibody levels over time and the continuous emergence of immune escape variants of concern (VOCs). As anti-spike serology is now widely available, it may be considered a useful tool to identify individuals needing an additional vaccine dose, i.e., to screen certain populations to identify those whose plasma antibody levels are too low to provide protection. However, no recommendations are currently available on this topic. We reviewed the relevant supporting and opposing arguments, including areas of uncertainty, and concluded that in most populations, spike serology should not be used to decide about the administration of a booster dose. The main counterarguments are as follows: correlates of protection are imperfectly characterised, essentially owing to the emergence of VOCs; spike serology has an intrinsic inability to comprehensively reflect the whole immune memory; and booster vaccines are now VOC-adapted, while the commonly available commercial serological assays explore antibodies against the original virus. [ABSTRACT FROM AUTHOR]

Background: Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods: The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 μg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 μg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (anti-spike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings: Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6-77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3-214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030-27 162), which increased to 37 460 ELU/mL (31 996-43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41-1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996-30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826-64 452), with a geometric mean fold change of 2·19 (1·90-2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37-14·32) and 15·90 (12·92-19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24-16·54] in the BNT162b2 group and 6·22 [3·90-9·92] in the mRNA-1273 group).Interpretation: Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose.Funding: UK Vaccine Task Force and National Institute for Health Research. [ABSTRACT FROM AUTHOR]

Abstract: Improving vaccine immunogenicity remains a major challenge in the fight against developing country diseases like malaria and AIDS. We describe a novel strategy to identify new DNA vaccine adjuvants. We have screened components of the Toll-like receptor signalling pathways for their ability to activate pro-inflammatory target genes in transient transfection assays and assessed in vivo adjuvant activity by expressing the activators from the DNA backbone of vaccines. We find that a robust increase in the immune response necessitates co-expression of two activators. Accordingly, the combination of tak1 and tram elicits synergistic reporter activation in transient transfection assays. In a mouse model this combination, but not the individual molecules, induced approximately twofold increases in CD8+ T-cell immune responses. These results indicate that optimal immunogenicity may require activation of distinct innate immune signalling pathways. Thus this strategy offers a novel route to the discovery of a new generation of adjuvants. [Copyright &y& Elsevier]

Background Successfully increasing cycling across a broad range of the population would confer important health benefits, but many potential cyclists are deterred by fears about traffic danger. Media coverage of road traffic crashes may reinforce this perception. As part of a wider effort to model the system dynamics of urban cycling, in this paper we examined how media coverage of cyclist fatalities in London changed across a period when the prevalence of cycling doubled. We compared this with changes in the coverage of motorcyclist fatalities as a control group. Methods Police records of traffic crashes (STATS19) were used to identify all cyclist and motorcyclist fatalities in London between 1992 and 2012. We searched electronic archives of London's largest local newspaper to identify relevant articles (January 1992–April 2014), and sought to identify which police-reported fatalities received any media coverage. We repeated this in three smaller English cities. Results Across the period when cycling trips doubled in London, the proportion of fatalities covered in the local media increased from 6% in 1992–1994 to 75% in 2010–2012. By contrast, the coverage of motorcyclist fatalities remained low (4% in 1992–1994 versus 5% in 2010–2012; p = 0.007 for interaction between mode and time period). Comparisons with other English cities suggested that the changes observed in London might not occur in smaller cities with lower absolute numbers of crashes, as in these settings fatalities are almost always covered regardless of mode share (79–100% coverage for both cyclist and motorcyclist fatalities). Conclusion In large cities, an increase in the popularity (and therefore ‘newsworthiness’) of cycling may increase the propensity of the media to cover cyclist fatalities. This has the potential to give the public the impression that cycling has become more dangerous, and thereby initiate a negative feedback loop that dampens down further increases in cycling. Understanding these complex roles of the media in shaping cycling trends may help identify effective policy levers to achieve sustained growth in cycling. [ABSTRACT FROM AUTHOR]

Abstract: Much recent public health research has emphasised the health impacts for young people of ‘active travel’ modes, typically defined as walking and cycling. Less research has focused on public transport modes. Drawing on qualitative data, we examine the links between bus travel and wellbeing in London, where young people currently have free bus travel. Our findings indicate that bus travel can be both a physically and socially active experience for young people. We suggest a more nuanced understanding of ‘active travel’ is now needed, alongside greater attention to urban public transport networks as key sites that impact on important determinants of wellbeing such as independent mobility and social inclusion. [Copyright &y& Elsevier]

In this article we examine equity in new active travel infrastructure in London, UK. We focus on Low Traffic Neighbourhoods (LTNs) introduced during Covid-19. These area-based schemes mainly involve 'modal filters' that restrict through motor traffic from residential streets within a neighbourhood. Such approaches to traffic management are traditional in the Netherlands, but are relatively novel in London and other global cities such as Barcelona. LTNs are often controversial, with one criticism being that they are implemented in affluent areas and hence benefit richer residents. London represents an excellent opportunity to investigate whether these rapidly introduced schemes have so far been equitably distributed. We focused on LTNs introduced between March and September 2020 and still present at the end of October 2020. Having generated datasets representing these new LTN locations and their boundary roads, we matched these to Output Areas (OAs, administrative areas containing around 300 residents). We then examined the extent to which LTN implementation was associated with age, ethnicity, disability, employment and car ownership (using Census 2011 data) and small-area deprivation (using the Index of Multiple Deprivation 2019). We estimated that 3.7% of all Londoners live inside a new LTN, and 8.9% live within 500 m walking distance of a new modal filter. Across London as a whole, people in the most deprived quarter of OAs were 2.5 times more likely to live in a new LTN, compared to Londoners in the least deprived quarter. While overall Black, Asian and Minority Ethnic (BAME) people were slightly more likely than White Londoners to live in a new LTN, this varied by ethnic group. Specifically, Black Londoners were somewhat more likely, and Asian Londoners somewhat less likely than White people to live in a new LTN. Car-free households were more likely to live in a new LTN. We also examined equity within London's districts, which lead on implementation of LTNs. In the median district, people in more deprived areas were more likely to live in an LTN than people in less deprived areas, suggesting that, on average, individual districts have prioritised their more deprived areas. However, in the median district, BAME residents were slightly less likely to live in an LTN than White residents. Across districts implementing LTNs there was wide variation, with some much more or less equitable than others. A third of districts implemented no LTNs at all. Finally, at the micro level, residents living in LTNs were demographically similar to neighbours living in OAs that touched an LTN boundary road. We conclude that LTN implementation has been broadly equitable at the city and micro levels, but the picture is more mixed at the district level, despite districts being encouraged to consider deprivation when planning LTN locations. Equity metrics should be used in policy and research to monitor and improve the distribution of active travel interventions. • Article examines equity of new Low Traffic Neighbourhood (LTN) implementation in London, UK, March–September 2020. • Across London, people in deprived areas were 2.5 times more likely to live in a new LTN than people in less deprived areas. • Across London, households without a car were 1.6 times more likely than car owners to live in an LTN. • At the micro-level, LTN residents were demographically similar to neighbours in nearby boundary areas. • London's devolved governance means equity at pan-London and micro-level can co-exist with a mixed picture at district-level. [ABSTRACT FROM AUTHOR]