Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses.

Systems vaccinology has defined molecular signatures and mechanisms of immunity to vaccination. However, comparative analysis of immunity to different vaccines is lacking. We integrated transcriptional data of over 3,000 samples, from 820 adults across 28 studies of 13 vaccines and analyzed vaccination-induced signatures of antibody responses. Most vaccines induced signatures of innate immunity and plasmablasts at days 1 and 7, respectively, after vaccination. However, the yellow fever vaccine induced an early transient signature of T and B cell activation at day 1, followed by delayed antiviral/interferon and plasmablast signatures that peaked at days 7 and 14-21, respectively. Thus, there was no evidence for a 'universal signature' that predicted antibody response to all vaccines. However, accounting for the asynchronous nature of responses, we defined a time-adjusted signature that predicted antibody responses across vaccines. These results provide a transcriptional atlas of immunity to vaccination and define a common, time-adjusted signature of antibody responses.

Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination.

Several studies have shown that the pre-vaccination immune state is associated with the antibody response to vaccination. However, the generalizability and mechanisms that underlie this association remain poorly defined. Here, we sought to identify a common pre-vaccination signature and mechanisms that could predict the immune response across 13 different vaccines. Analysis of blood transcriptional profiles across studies revealed three distinct pre-vaccination endotypes, characterized by the differential expression of genes associated with a pro-inflammatory response, cell proliferation, and metabolism alterations. Importantly, individuals whose pre-vaccination endotype was enriched in pro-inflammatory response genes known to be downstream of nuclear factor-kappa B showed significantly higher serum antibody responses 1 month after vaccination. This pro-inflammatory pre-vaccination endotype showed gene expression characteristic of the innate activation state triggered by Toll-like receptor ligands or adjuvants. These results demonstrate that wide variations in the transcriptional state of the immune system in humans can be a key determinant of responsiveness to vaccination.

The Immune Signatures data resource, a compendium of systems vaccinology datasets.

Vaccines are among the most cost-effective public health interventions for preventing infection-induced morbidity and mortality, yet much remains to be learned regarding the mechanisms by which vaccines protect. Systems immunology combines traditional immunology with modern 'omic profiling techniques and computational modeling to promote rapid and transformative advances in vaccinology and vaccine discovery. The NIH/NIAID Human Immunology Project Consortium (HIPC) has leveraged systems immunology approaches to identify molecular signatures associated with the immunogenicity of many vaccines. However, comparative analyses have been limited by the distributed nature of some data, potential batch effects across studies, and the absence of multiple relevant studies from non-HIPC groups in ImmPort. To support comparative analyses across different vaccines, we have created the Immune Signatures Data Resource, a compendium of standardized systems vaccinology datasets. This data resource is available through ImmuneSpace, along with code to reproduce the processing and batch normalization starting from the underlying study data in ImmPort and the Gene Expression Omnibus (GEO). The current release comprises 1405 participants from 53 cohorts profiling the response to 24 different vaccines. This novel systems vaccinology data release represents a valuable resource for comparative and meta-analyses that will accelerate our understanding of mechanisms underlying vaccine responses.

Single-cell immunology of SARS-CoV-2 infection.

Gaining a better understanding of the immune cell subsets and molecular factors associated with protective or pathological immunity against severe acute respiratory syndrome coronavirus (SARS-CoV)-2 could aid the development of vaccines and therapeutics for coronavirus disease 2019 (COVID-19). Single-cell technologies, such as flow cytometry, mass cytometry, single-cell transcriptomics and single-cell multi-omic profiling, offer considerable promise in dissecting the heterogeneity of immune responses among individual cells and uncovering the molecular mechanisms of COVID-19 pathogenesis. Single-cell immune-profiling studies reported to date have identified innate and adaptive immune cell subsets that correlate with COVID-19 disease severity, as well as immunological factors and pathways of potential relevance to the development of vaccines and treatments for COVID-19. For facilitation of integrative studies and meta-analyses into the immunology of SARS-CoV-2 infection, we provide standardized, download-ready versions of 21 published single-cell sequencing datasets (over 3.2 million cells in total) as well as an interactive visualization portal for data exploration.

Drainage, irrigation and fibrinolytic therapy (DRIFT) for posthaemorrhagic ventricular dilatation: 10-year follow-up of a randomised controlled trial.

BACKGROUND: Progressive ventricular dilatation after intraventricular haemorrhage (IVH) in preterm infants has a very high risk of severe disability and death. Drainage, irrigation and fibrinolytic therapy (DRIFT), in a randomised controlled trial (RCT), reduced severe cognitive impairment at 2 years. OBJECTIVE: To assess if the cognitive advantage of DRIFT seen at 2 years persisted until school age. PARTICIPANTS: The RCT conducted in four centres recruited 77 preterm infants with IVH and progressive ventricular enlargement over specified measurements. Follow-up was at 10 years of age. INTERVENTION: Intraventricular injection of a fibrinolytic followed by continuous lavage, until the drainage was clear, and standard care consisting of control of expansion by lumbar punctures and if expansion persisted via a ventricular access device. PRIMARY OUTCOME: Cognitive quotient (CQ), derived from the British Ability Scales and Bayley III Scales, and survival without severe cognitive disability. RESULTS: Of the 77 children randomised, 12 died, 2 could not be traced, 10 did not respond and 1 declined at 10-year follow-up. 28 in the DRIFT group and 24 in the standard treatment group were assessed by examiners blinded to the intervention. The mean CQ score was 69.3 (SD=30.1) in the DRIFT group and 53.7 (SD=35.7) in the standard treatment group (unadjusted p=0.1; adjusted p=0.01, after adjustment for the prespecified variables sex, birth weight and IVH grade). Survival without severe cognitive disability was 66% in the DRIFT group and 35% in the standard treatment group (unadjusted p=0.019; adjusted p=0.003). CONCLUSION: DRIFT is the first intervention for posthaemorrhagic ventricular dilatation to objectively demonstrate sustained cognitive improvement. TRIAL REGISTRATION NUMBER: ISRCTN80286058.

From problem people to addictive products: a qualitative study on rethinking gambling policy from the perspective of lived experience.

BACKGROUND: Previous research has shown that government and industry discussions of gambling may focus on personal responsibility for gambling harm. In Australia, these discussions have largely excluded people with lived experience of problem gambling, including those involved in peer support and advocacy. METHODS: We conducted 26 in-depth interviews with people with current or previous problem gambling on electronic gaming machines (EGMs) involved in peer support and advocacy activities, using an approach informed by Interpretive Policy Analysis and Constructivist Grounded Theory. RESULTS: Participants perceived that government and industry discussed gambling as safe and entertaining with a focus on personal responsibility for problem gambling. This focus on personal responsibility was perceived to increase stigma associated with problem gambling. In contrast, they described gambling as risky, addictive and harmful, with problem gambling resulting from the design of EGMs. As a result of their different perspectives, participants proposed different interventions to reduce gambling harm, including reducing accessibility and making products safer. CONCLUSIONS: Challenging the discourses used by governments and industry to describe gambling, using the lived experience of people with experience of gambling harm, may result in reduced stigma associated with problem gambling, and more effective public policy approaches to reducing harm.

How a concerned family member, friend or member of the public can help someone with gambling problems: a Delphi consensus study.

BACKGROUND: Gambling is an enjoyable recreational pursuit for many people. However, for some it can lead to significant harms. The Delphi expert consensus method was used to develop guidelines for how a concerned family member, friend or member of the public can recognise the signs of gambling problems and support a person to change their gambling. METHODS: A systematic review of websites, books and journal articles was conducted to develop a questionnaire containing items about the knowledge, skills and actions needed for supporting a person with gambling problems. These items were rated over three rounds by two international expert panels comprising people with a lived experience of gambling problems and professionals who treat people with gambling problems or research gambling problems. RESULTS: A total of 66 experts (34 with lived experience and 32 professionals) rated 412 helping statements according to whether they thought the statements should be included in these guidelines. There were 234 helping statements that were endorsed by at least 80 % of members of both of the expert panels. These endorsed statements were used to develop the guidelines. CONCLUSION: Two groups of experts were able to reach substantial consensus on how someone can recognise the signs of gambling problems and support a person to change.

How the causes, consequences and solutions for problem gambling are reported in Australian newspapers: a qualitative content analysis.

OBJECTIVE: To inform public health approaches to problem gambling by examining how the news media covers problem gambling, with a particular focus on the causes, consequences and solutions to problem gambling, and the 'actors' and sources who influence media coverage. METHODS: A qualitative content analysis guided by framing theory analysed coverage of problem gambling in Australian newspapers in the period 1 July 2011 to 30 June 2012. RESULTS: Solutions to problem gambling were more frequently discussed than causes and consequences. A focus on the responsibility of individuals was preferred to reporting that focused on broader social, ecological, and industry determinants of problem gambling. Reporting was highly politicised, with politicians frequently quoted and political issues frequently discussed. In contrast, the community sector, health professionals and problem gamblers were rarely quoted. CONCLUSIONS AND IMPLICATIONS: This analysis has revealed the need for a more proactive, coordinated approach to the media by both public health researchers and health groups. The establishment of a gambling-specific coalition to push for evidence-based reform is recommended.

The King's Outcome Scale for Childhood Head Injury and injury severity and outcome measures in children with traumatic brain injury.

The aim of this study was to relate discharge King's Outcome Scale for Childhood Head Injury (KOSCHI) category to injury severity and detailed outcome measures obtained in the first year post-traumatic brain injury (TBI). We used a prospective cohort study. Eighty-one children with TBI were studied: 29 had severe, 15 moderate, and 37 mild TBI. The male:female ratio was 1.8:1. The mean age was 11 years 10 months (SD 3.6, range 5-16y). Discharge KOSCHI categories were good (n=34), moderate (n=39), severe (n=6), and unclassifiable (n=2). KOSCHI category correlated strongly with admission Glasgow Coma Score, length of hospital stay, and post-traumatic amnesia. It also correlated significantly with Verbal IQ and Performance IQ (Wechsler); measures of attention; health status (Health Utilities Index [HUI]); health-related quality of life (Pediatric Quality of Life Inventory [PedsQL]); depressive symptoms (Birleson Depression Scale) assessed within 3 months postTBI; and with Verbal IQ, selective attention (map mission), and HUI and PedsQL domains assessed at least 6 months post-TBI discharge. KOSCHI did not correlate with behaviour or executive function. We conclude that the KOSCHI scored at hospital discharge correlates with severity of injury and some cognitive, health status, and HRQL outcomes early after TBI. It is not helpful at predicting later difficulties, or behavioural and emotional problems.

"I need to talk about it": a qualitative analysis of trauma-exposed women's reasons for treatment choice.

A significant proportion of individuals suffering from posttraumatic stress disorder do not seek or receive effective treatment. Understanding the reasons why an individual chooses to seek treatment or prefers one treatment to another is a critical step to improve treatment seeking. To begin to understand these reasons, we conducted a qualitative analysis of the reasons women gave for choosing a cognitive-behavioral treatment, prolonged exposure (PE), or a pharmacological treatment, sertraline (SER). A community sample of women with trauma histories were asked to view standardized rationales, to choose among PE, SER, or no treatment, and to give 5 reasons for their choice. Women indicated that they were more likely to prefer the psychotherapy to the medication. Across reasons given, the most commonly cited reason for treatment preference highlighted why or how the treatment worked (e.g., I need to talk about it); and this reason emerged as the strongest predictor of preference for PE. Understanding this role of perceived treatment mechanism may aid clinicians and public health policy officials to identify and address help-seeking barriers regarding treatment.