Sex Differences in Vaccine-Specific and Heterologous Immunity Following Administration of Measles and /or DtwP Vaccines to Nine Month-Old Gambian Infants

The expanded programme of immunization was introduced in The Gambia over 30 years ago, using empirically developed vaccines with limited understanding of exactly how they work. Observational studies showing vaccines have heterologous beneficial or deleterious effects on disease susceptibility, dependent on sex, have been controversial, with no immunological data to support these epidemiological findings. The live measles vaccine (MV) seems to have beneficial protective effects, while diphtheria, tetanus, whole cell pertussis (DTwP) vaccine increases disease susceptibility, both effects being more prominent in females. These effects are modified when the vaccines are given simultaneously. This thesis describes the results of a randomized trial primarily aimed at studying the heterologous effects of MV and DTwP vaccination of 9 month old Gambian infants. Assays included multiplex cytokine analysis of culture supernatants, flow cytometric intracellular staining, vaccine antibody assays, and whole transcriptome microarray analysis. Measles and DTwP antibodies were not affected by combining vaccines or by gender. When DTwP is given with MV, the measles-specific response was skewed away from a protective CD8 IFN-γ response, while TT responses become more pro-inflammatory suggesting that MV has an adjuvant effect on DTwP immunity. A striking finding was the immunosuppressive effect of DTwP, particularly in females. There was a reduction in pro-inflammatory cytokines and reduced IFN-γ:IL-10 ratios in aCD3/28 cultures, alongside down-regulated interferon response gene pathways, and increased innate IL-10 production in DTwP vaccinated females. By contrast, DTwP vaccinated males a more pro-inflammatory profile than females with only upregulated genes post-vaccination. Males vaccinated with MV+DTwP were less pro-inflammatory than females, and had only down-regulated genes suggesting this combination had opposite effects in males and females. The results provide plausible immunological explanations for the observed beneficial and deleterious effects of MV and DTwP respectively. These will now need to be tested in carefully designed prospective studies

Organisational drivers of performance in mental health providers

Purpose: This study aims to compare and contrast the core organisational processes across high and low performing mental health providers in the English National Health Service (NHS).Design/methodology/approach: A multiple case study qualitative design incorporating a full sample of low and high performing mental health providers.Findings: This study suggests that the organisational approaches used to govern and manage mental health providers are associated with their performance, and the study’s findings give clues as to what areas might need attention. They include, but are not limited to: developing appropriate governance frameworks and organisational cultures, ensuring that staff across the organisation feel “psychologically safe” and able to speak up when they see things that are going wrong; a focus on enhancing quality of services rather than prioritising cost-reduction; investing in new technology and digital applications; and nurturing positive inter-organisational relationships across the local health economy.Originality/value: Highlights considerable divergence in organisation and management practices that are associated with the performance of mental health trusts in the English NH

Nutritional Status of Children in Displacement Camps in Sierra Leone

Civil wars have resulted in the displacement of millions of people worldwide and have forced many into temporary displacement camps. Sometimes, most are caught in prolonged and overcrowded refugee camps, which provide ideal grounds for the transmission of diseases, increased risk for acute respiratory infections, diarrhoeal diseases, and malnutrition. In this study, stunting, under nutrition, and wasting were measured among 454 children under the age of 10 years in four internally displaced persons (IDP) camps. Stunting was found to be the most common nutritional abnormality in all four IDP camps with the highest prevalence rate (29.3%) in the Trade Center Camp and lowest (14.2%) in the National Workshop Camp. This study indicates that forced internal displacement results in high prevalence of stunting, wasting and underweight among children.Key Words: Nutritional status, Children, Displacement, Sierra Leone

Survey of drinking water access points in the Sierra Leone Districts of Bo, Koinadugu and Tonkolili 2010/2011

An independent study conducted by a French NGO in Sierra Leone at the end of 2010 surveyed all existing water access points across three districts, documenting in detail the quality of the 2,859 structures identified. Only 30% of the structures in place were found to be capable of delivering access to safe water throughout the year. Analysis of the results indicate that the low level of functionality reflects a supply-driven approach, a decrease in the quality of construction and an absence of attention to socio-organisational factors long known to be absolutely essential to the proper functioning of the systems. Given the critical importance of access to safe drinking water and the disparity between the stated intentions of donor organisations and the realities on the ground, the survey provides a telling picture that could be used as a basis for change and increased effectiveness

Changing leadership, management and culture in mental health trusts

Purpose - To explore how leadership, management practices and organisational cultures have changed in low and high performing mental health providers between 2015 and 2020 in the English National Health Service (NHS). Design/methodology/approach - We used a qualitative case study design comprising a purposeful sample of two low performing and two high performing mental health providers, based on . The main form of data collection was semistructured interviews with 60 key informants (mostly internal to the organisation with some external informants from local Clinical Commissioning Groups). Findings - We found major differences regarding leadership, management and organisational culture between low and high performing mental health providers in 2015/2016, and that the differences had diminished considerably by 2019/20. In 2015/16, low performing providers were characterised by a ‘top-down’ style of leadership, centralised decision-making, and ‘blame cultures’. In contrast, the high performing providers were characterised as having more distributed, collaborative and inclusive styles of leadership/management, with open and supportive cultures. As the low performing providers changed and adapted their styles of leadership and management and organisational culture over the five-year period, they more closely resembled those of the high performing trusts. Originality/value - This is the first study to explore the relationship between changing organisational factors (leadership, culture, management practices) and the performance of mental health care providers. It provides evidence that it is possible for radical changes in leadership, management and organisational culture to be enacted over a relatively short period of time and that such changes may help low performing providers to turnaround their underperformance

IT and the Quality and Efficiency of Mental Health Care in a Time of COVID-19: Case Study of Mental Health Providers in England

Background: In England, COVID-19 has significantly affected mental health care and tested the resilience of health care providers. In many areas, the increased use of IT has enabled traditional modes of service delivery to be supported or even replaced by remote forms of provision. Objective: This study aimed to assess the use and impact of IT, in remote service provision, on the quality and efficiency of mental health care during the pandemic. We drew on sociotechnical systems theory as a conceptual framework to help structure the gathering, analysis, and interpretation of data. Methods: We conducted a national scoping survey that involved documentary analysis and semistructured interviews with 6 national stakeholders and case studies of 4 purposefully selected mental health providers in England involving interviews with 53 staff members. Results: Following the outbreak of COVID-19, mental health providers rapidly adjusted their traditional forms of service delivery, switching to digital and telephone consultations for most services. The informants provided nuanced perspectives on the impact on the quality and efficiency of remote service delivery during the pandemic. Notably, it has allowed providers to attend to as many patients as possible in the face of COVID-19 restrictions, to the convenience of both patients and staff. Among its negative effects are concerns about the unsuitability of remote consultation for some people with mental health conditions and the potential to widen the digital divide and exacerbate existing inequalities. Sociotechnical systems theory was found to be a suitable framework for understanding the range of systemic and sociotechnical factors that influence the use of technology in mental health care delivery in times of crisis and normalcy. Conclusions: Although the use of IT has boosted mental health care delivery during the pandemic, it has had mixed effects on quality and efficiency. In general, patients have benefited from the convenience of remote consultation when face-to-face contact was impossible. In contrast, patient choice was often compromised, and patient experience and outcomes might have been affected for some people with mental health conditions for which remote consultation is less suitable. However, the full impact of IT on the quality and efficiency of mental health care provision along with the systemic and sociotechnical determinants requires more sustained and longitudinal research

Co-creating sociotechnical visions for a circular metal economy transition in the UK

The UK government's target of achieving net-zero emissions by 2050 has created an urgent need for decarbonization and the transition towards a circular metal economy (CME). The production of steel and aluminium, critical components of modern industry, contribute significantly to greenhouse gas emissions and are the focus of this paper. This paper explores the barriers and enablers involved in moving towards a CME. Although recycling is an essential strategy for metal recovery, it may not suffice to achieve the UK government's net-zero objectives. The paper suggests twelve preferred visions for a CME, encompassing the entire metal value chain, co-created through collaboration with over one hundred industry and academic experts. These visions can serve as a foundation for co-design workshops for academics to investigate additional barriers and enablers within the metal sector. Within corporate management, these visions can be used to set targets and guide decision-making towards specific circular and sustainable goals. Finally, policymakers can use these visions to develop a roadmap or comprehend the implications and rebound effects of a CME transition for the UK.UKRI National Interdisciplinary Circular Economy Research programme (NICER)

2050 Circular Metal Visions

This progress report was produced within the UKRI Interdisciplinary Centre for Circular Metals (Principal Investigator Prof Zhongyun Fan), as part of the activities of WP3 ‘Circular Business’ (led by Prof Janet Godsell) and work stream WP3.1 ‘Circular business model innovation’ (led by Dr Fabrizio Ceschin).This progress report presents some initial findings of the WP3 ’Circular Business’ of the UKRI Interdisciplinary Centre for the Circular Metals. The aim of the centre is to transform the metals industry and make the UK the first country in the world to have a fully circular metals system. The purpose of this progress report is to present a set of visions of how circular economy can transform the metal value chain in the long term. The progress report presents 12 visions for 2050 and discusses the most significant challenges and opportunities that might respectively hinder and support the shift to those visions. The progress report is the result of research activities that brought together leading experts from academia, industry, and government to explore how the UK could transition to a circular metal economy

The impact of training on self-reported performance in reproductive, maternal, and newborn health service delivery among healthcare workers in Tanzania: a baseline- and endline-survey

Background: Delivery of quality reproductive health services has been documented to depend on the availability of healthcare workers who are adequately supported with appropriate training. However, unmet training needs among healthcare workers in reproductive, maternal, and newborn health (RMNH) in low-income countries remain disproportionately high. This study investigated the effectiveness of training with onsite clinical mentorship towards self-reported performance in RMNH among healthcare workers in Mwanza Region, Tanzania. Methods: The study used a quasi-experimental design with pre-and post-intervention evaluation strategy. The baseline was compared with two endline groups: those with intervention (training and onsite mentorship) and those without. The differences among the three groups in the sociodemographic characteristics were analyzed by using chi-square test for categorical variables, independent-sample t-test for continuous variables and Mann-Whitney U test for ordinal or skewed continuous data. The independent sample t-test was used to determine the effect of the intervention by comparing the computed self-reported performance on RMNH services between the intervention and control groups. The paired-samples t-test was used to measure the differences between before and after intervention groups. Significance was set at a 95% confidence interval with p ≤ 0.05. Results: The study included a sample of 216 participants with before and after intervention groups comprising of 95 (44.0%) and 121 (56.0%) in the control group. The comparison between before and after intervention groups revealed a statistically significant difference (p ≤ 0.05) in all the dimensions of the self-reported performance scores. However, the comparison between intervention groups and controls indicated a statistical significant difference on intra-operative care (t = 3.10, df = 216, p = 0.002), leadership skills (t = 1.85, df = 216, p = 0.050), Comprehensive emergency obstetric and newborn care (CEMONC) (t = 34.35, df = 216, p ≤ 0.001), and overall self-reported performance in RMNH (t = 3.15, df = 216, p = 0.002). Conclusions: This study revealed that the training and onsite clinical mentorship to have significant positive changes in self-reported performance in a wide range of RMNH services especially on intra-operative care, leadership skills and CEMONC. However, further studies with rigorous designs are warranted to evaluate the long-term effect of such training programs on RMNH outcomes

Sex-differential non-vaccine specific immunological effects of diphtheria-tetanus-pertussis and measles vaccination

Vaccines can have nontargeted heterologous effects that manifest as increased protection against nonvaccine infections, as described for measles vaccine (MV), or increased susceptibility to infections and death, as described following diphtheria-tetanus-whole cell pertussis (DTP) vaccination. The mechanisms are unknown, and high-quality immunological studies are lacking. This study was designed to investigate the heterologous effects of MV and DTP in 302 Gambian infants. The results support a sex-differential immunosuppressive effect of DTP on innate proinflammatory responses and T-cell immunity. Males but not females receiving MV had enhanced proinflammatory innate responses. The results point to modified signaling via Toll-like receptor 4 (TLR4) as a possible mechanism for the effects on innate immunity. When both vaccines were administered together, purified protein derivative responses were enhanced in females but downregulated in males. Collectively, these data indicate immunological effects that could account for heterologous effects of MV and DTP, to take forward into prospective trials