Correlates of Zero-Dose Vaccination Status Among Children Aged 12-59 Months in Sub-Saharan Africa: A Multilevel Analysis of Individual and Contextual Factors

Despite ongoing efforts to improve childhood vaccination coverage, including in hard-to-reach and hard-to-vaccinate communities, many children in sub-Saharan Africa (SSA) remain unvaccinated. Considering recent goals set by the Immunization Agenda 2030 (IA2030), including reducing the number of zero-dose children by half, research that goes beyond coverage to identify populations and groups at greater risk of being unvaccinated is urgently needed. This is a pooled cross-sectional study of individual- and country-level data obtained from Demographic and Health Surveys Program and two open data repositories. The sample includes 43,131 children aged 12–59 months sampled between 2010 and 2020 in 33 SSA countries. Associations of zero-dose status with individual and contextual factors were assessed using multilevel logistic regression. 16.5% of children had not received any vaccines. Individual level factors associated lower odds of zero-dose status included mother’s primary school or high school education, employment, use of antenatal care services and household wealth. Compared to children in countries with lower GDP, children in countries with relatively high GDP had nearly four times greater odds of being unvaccinated. Both individual and contextual factors are correlated with zero-dose status in SSA. Our results can inform efforts to identify and reach children who have not received any vaccines

Temporal Geospatial Analysis of COVID-19 Pre-infection Determinants of Risk in South Carolina

Disparities and their geospatial patterns exist in morbidity and mortality of COVID-19 patients. When it comes to the infection rate, there is a dearth of research with respect to the disparity structure, its geospatial characteristics, and the pre-infection determinants of risk (PIDRs). This work aimed to assess the temporal–geospatial associations between PIDRs and COVID-19 infection at the county level in South Carolina. We used the spatial error model (SEM), spatial lag model (SLM), and conditional autoregressive model (CAR) as global models and the geographically weighted regression model (GWR) as a local model. The data were retrieved from multiple sources including USAFacts, U.S. Census Bureau, and the Population Estimates Program. The percentage of males and the unemployed population were positively associated with geodistributions of COVID-19 infection (p values \u3c 0.05) in global models throughout the time. The percentage of the white population and the obesity rate showed divergent spatial correlations at different times of the pandemic. GWR models fit better than global models, suggesting nonstationary correlations between a region and its neighbors. Characterized by temporal–geospatial patterns, disparities in COVID-19 infection rate and their PIDRs are different from the mortality and morbidity of COVID-19 patients. Our findings suggest the importance of prioritizing different populations and developing tailored interventions at different times of the pandemic

Family Poverty Affects the Rate of Human Infant Brain Growth

Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems

Stakeholder Influences on the Design of Firms’ Environmental Practices

While prior literature has emphasized that stakeholders can influence a firm's decision to adopt environmental practices that lead to competitive advantage, most scholarship has assumed that stakeholders influence the design of firms' environmental practices similarly. We challenge this notion and suggest that stakeholders affect not only the decision to adopt environmental practices, but also managerial decisions about the design of these practices. We consider the case of firms' strategic decisions about the design of their environmental practices, and in particular their degree of comprehensiveness and visibility. We then develop a classification of four design strategies: movers and shakers, backroom operators, wannabes, and passivists. Using multinomial regression techniques for a sample of more than 1700 firms worldwide, our research shows that while stakeholders exert pressures on firms, managers' perceptions of these pressures vary, and these variations appear to influence the design of their environmental practices. These findings offer important evidence that the scope of stakeholders' influence appears more far reaching (and nuanced) than previously considered. Managers who respond to these influences may therefore be in a better position to satisfy stakeholder expectations, thus enhancing their organization's overall credibility

Sports events and interaction among spectators: examining antecedents of spectators’ value creation

Research question: Spectating at sports events comprises on-pitch and off-pitch benefits. Value may also derive from spectator-to-spectator interaction, however, we do not know whether all types of interaction have similar effects on value creation and subsequent word-of-mouth (WOM) behaviours. We investigate two types of spectator-to-spectator interaction – between known/familiar others, and between unknown-others. We study their effects within a framework grounded in Customer Dominant Logic and sport value framework, integrating on-pitch sport performance, off-pitch service quality, overall satisfaction, team identification and WOM intention. Research methods: Hypotheses were tested using a survey of 1002 spectators of a British Premier League football club. Respondents were asked about the last game they attended. Data were analysed using Structural Equations Modelling and PROCESS analysis. Results and findings: Customer-to-customer interaction was antecedent to overall satisfaction and team identification. Satisfaction and team identification led to WOM intention, with team identification having greater effect. Evaluation of on-pitch performance (the football match) influenced overall satisfaction more than off-pitch service quality. The study contributes to knowledge in finding that customer-to-customer interaction with familiar accompaniers influenced satisfaction more than interaction with anonymous-other spectators. However, the latter contributed more to team identification and indirectly to WOM. Implications: The study highlights the importance to sports events organisers of facilitating customer-to-customer interaction. While promotion of many sports events focuses on game performance, this study highlights the importance of promoting the social benefits of attendance in increasing positive WOM. Suggestions are made, including provision of social media platforms within events to promote interaction among spectators

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme