Insufficient Sleep and Behavioral Health in the Military: A 5-Country Perspective.

PURPOSE OF REVIEW: The goal of this paper was to highlight the degree to which sleep, behavioral health, and leader involvement were interrelated using data from militaries in five English-speaking countries: Australia, Canada, New Zealand, the UK, and the United States. RECENT FINDINGS: Many service members reported sleeping fewer than the recommended 7 h/night: 34.9%, 67.2%, and 77.2% of respondents from New Zealand, Canada, and the United States, respectively. Countries reporting shorter sleep duration also reported fewer insomnia-related difficulties, likely reflecting higher sleep pressure from chronic sleep loss. Across all countries, sleep problems were positively correlated with behavioral health symptoms. Importantly, leader promotion of healthy sleep was positively correlated with more sleep and negatively correlated with sleep problems and behavioral health symptoms. Insufficient sleep in the military is ubiquitous, with serious implications for the behavioral health and functioning of service members. Leaders should attend to these risks and examine ways to promote healthy sleep in service members.

Assessing Military Mental Health during the Pandemic: A Five Country Collaboration.

PURPOSE OF REVIEW: Members of a technical panel representing Australia, Canada, New Zealand, the UK, and the US collaborated to develop surveys designed to provide military leaders with information to guide decisions early in the COVID-19 pandemic. The goal of this paper is to provide an overview of this collaboration and a review of findings from the resulting body of work. RECENT FINDINGS: While surveys pointed to relatively favorable mental health and perceptions of leadership among military personnel early in the pandemic, these observations did not reflect the experiences of personnel deployed in COVID-19 response operations, nor were these observations reflective of later stages of the pandemic. Establishing and leveraging networks that enable the rapid development of employee surveys and sharing of results can serve as a pathway for empowering military leaders in times of crisis. Organizational support and leadership decisions are especially critical for maintaining well-being among personnel during crises.

Student nurse retention. Lived experience of mature female students on a UK Bachelor of Nursing (Adult) programme: An interpretative phenomenological analysis.

AIMS: To explore the lived experiences of mature female students undertaking a Bachelor of Nursing (Adult) programme in the UK, to gain insight into the challenges and barriers faced by students and investigate the factors that support students who have considered leaving, to stay and continue with their studies. BACKGROUND: There is a global shortage of nurses and challenges exist in ensuring that enough nurses are available to provide care in the complex and rapidly changing care environments. Initiatives introduced to increase the number of Registered Nurses (RN), include increasing the number of students enrolled on pre-registration nursing programmes. However, the success of this intervention is contingent on the number of students who go on to complete their course. DESIGN: This qualitative study employed Interpretative Phenomenological Analysis (IPA), which provided a methodological framework and analytical approach to enable an exploration of participants' individual and shared lived experiences. METHODS: Eight female, mature students at the end of their second year of a Bachelor of Nursing (Adult) programme at a Higher Education Institution in South Wales participated in semi-structured, face-to-face interviews, which were analysed idiographically before group-level analysis was undertaken. FINDINGS: The analysis revealed three superordinate themes: 'Ambition to become a Registered Nurse'; 'Jugging Roles' and 'Particular Support Needs for a Particular Student'. CONCLUSION: Each student had a unique history, their past and present social and psychological experiences were multifaceted and complex. These differences resulted in varying degrees of resilience and motivations to continue their studies. These findings are important for ensuring that services develop and provide effective support to maximize retention and, ultimately, increase the number of students entering the RN workforce. PATIENT OF PUBLIC CONTRIBUTION: No patient or public contribution. IMPACT STATEMENT: This research expands on current literature regarding the needs of mature female students, a growing student nurse demographic. Every student had a dynamic set of circumstances and demonstrated that the identification of 'at-risk' students, purely based on demographics or information on a Curriculum Vitae, is problematic and potentially futile. This knowledge could be used to tailor University support systems and inform curriculum development and support systems for maximizing student retention. These findings are important for ensuring that services continue to develop and provide effective support to maximize retention and completion and, ultimately, increase the number of students entering the Nursing and Midwifery Council register.

Which interventions improve HPV vaccination uptake and intention in children, adolescents and young adults? An umbrella review.

BACKGROUND: Human papillomavirus (HPV) vaccination offers protection against the virus responsible for cervical, oropharyngeal, anal, vulval and penile cancers. However, there is considerable variation across, and even within, countries as to how HPV vaccination is offered and accepted. This review aimed to identify what interventions exist to promote uptake and how effective they are. METHODS: We conducted an umbrella review using the JBI (Joanna Briggs Institute) methodology to evaluate routine or catch-up interventions to increase HPV vaccination uptake and/or intention for children aged 9 years and older, adolescents and young adults up to 26. Comprehensive searches for English language quantitative systematic reviews, published between January 2011 and July 2021, were conducted across five databases. After reviewing titles and abstract, relevant papers were independently assessed in detail. MAIN RESULTS: From 1046 records identified, 10 articles were included in the review. They reported on 95 randomised controlled trials, 28 quasi-experimental studies, 14 cohort studies, 6 non-randomised pretest/post-test studies with control groups, 5 single-group pretest/post-test studies, 1 single-group post-test study and 1 randomised longitudinal study. Some interventions promoted change at the individual, community or organisational level, while others used a multicomponent approach. Face-to-face presentations, printed information and supplementing both strategies with additional components appear effective at increasing vaccination intention, while reminders and multicomponent strategies, especially ones that include some intervention aimed at provider level, appear effective at increasing vaccination uptake. Interventions that did not lead to an improvement in HPV vaccination intention or uptake varied in design and impacts were inconsistent across children/adolescents, young adults or parents. CONCLUSION: The evidence suggests that there is no single solution to increasing vaccination uptake and that different approaches may be better suited to certain populations. However, generalisations are limited by poor reporting and a paucity of studies beyond the USA. Further high-quality studies, therefore, are needed to understand how best to increase HPV vaccination uptake in different target populations.

Inducible ablation of CD11c+ cells to determine their role in skin wound repair.

Whether resident and recruited myeloid cells may impair or aid healing of acute skin wounds remains a debated question. To begin to address this, we examined the importance of CD11c+ myeloid cells in the early activation of skin wound repair. We find that an absence of CD11c+ cells delays wound closure and epidermal proliferation, likely due to defects in the activation of the IL-23-IL-22 axis that is required for wound healing.

Nursing and values-based leadership: A literature review.

AIM: To explore literature that supports an understanding of values-based leadership in nursing. BACKGROUND: Understanding values-based leadership in nursing means understanding several leadership theories such as authentic, servant and congruent leadership. EVALUATION: Electronic databases were systematically searched to locate studies with the terms values-based, authentic, servant and congruent leadership. The literature was assessed with the Joanna Briggs Institute Critical Appraisal Tools and the Preferred Reporting Items for Systematic Reviews and meta-analysis approach and a thematic analysis. KEY ISSUES: Existing evidence focuses on specific perspectives within three dominant leadership approaches under the umbrella of values-based leadership: authentic, servant and congruent leadership. Limited literature suggests that values-based leadership can support professional collaboration, enhanced trust and voice for nurses, support for staff well-being, empowerment, job satisfaction, patient-focused outcomes and quality care. CONCLUSIONS: A dearth of empirical literature concerning values-based leadership and nursing exists. Evidence suggests that authentic, servant and congruent leadership correlate with values-based leadership theories and core nursing values. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers should recognize the potential benefits of a values-based leadership approach for staff well-being, enhanced professional collaboration and the nurses voice, improved insight into clinical leadership attributes and improvements in quality patient care.

Resilience and attitudes toward help-seeking as correlates of psychological well-being among a sample of New Zealand Defence Force personnel.

Research is needed to examine factors that contribute to psychological well-being among military service members. This study examined associations between various indices of psychological well-being, resilience, and help-seeking stigma among New Zealand Defence Force (NZDF) personnel (N = 2,805). Participants completed self-report measures of psychological well-being, resilience, help-seeking stigma, and past-year help-seeking behaviors. Greater resilience and a lower degree of help-seeking stigma were each significantly associated with better psychological well-being (i.e., greater psychological flourishing, less psychological distress, and better overall mental health). Though effects were relatively small, engagement in help-seeking behaviors moderated the relationship between (1) greater resilience and less psychological distress and (2) greater resilience and better overall mental health, such that these relationships were stronger among those who had sought help for their mental health in the past year. Findings suggest that greater resilience and less mental health help-seeking stigma may independently contribute to better psychological well-being among NZDF personnel; thus, enhancing resilience and reducing help-seeking stigma may serve to promote psychological well-being in this population. Improving resilience among NZDF personnel who seek help, in particular, may contribute to better psychological well-being. However, longitudinal research among service members is needed to establish a temporal relationship between these constructs.

Tumor-Resident Dendritic Cells and Macrophages Modulate the Accumulation of TCR-Engineered T Cells in Melanoma.

Ongoing clinical trials explore T cell receptor (TCR) gene therapy as a treatment option for cancer, but responses in solid tumors are hampered by the immunosuppressive microenvironment. The production of TCR gene-engineered T cells requires full T cell activation in vitro, and it is currently unknown whether in vivo interactions with conventional dendritic cells (cDCs) regulate the accumulation and function of engineered T cells in tumors. Using the B16 melanoma model and the inducible depletion of CD11c+ cells in CD11c.diphtheria toxin receptor (DTR) mice, we analyzed the interaction between tumor-resident cDCs and engineered T cells expressing the melanoma-specific TRP-2 TCR. We found that depletion of CD11c+ cells triggered the recruitment of cross-presenting cDC1 into the tumor and enhanced the accumulation of TCR-engineered T cells. We show that the recruited tumor cDCs present melanoma tumor antigen, leading to enhanced activation of TCR-engineered T cells. In addition, detailed analysis of the tumor myeloid compartment revealed that the depletion of a population of DT-sensitive macrophages can contribute to the accumulation of tumor-infiltrating T cells. Together, these data suggest that the relative frequency of tumor-resident cDCs and macrophages may impact the therapeutic efficacy of TCR gene therapy in solid tumors.

Treatment of military-related post-traumatic stress disorder: challenges, innovations, and the way forward.

Post-traumatic stress disorder (PTSD) is one of the common mental disorders in military and veteran populations. Considerable research and clinical opinion has been focused on understanding the relationship between PTSD and military service and the implications for prevention, treatment, and management. This paper examines factors associated with the development of PTSD in this population, considers issues relating to engagement in treatment, and discusses the empirical support for best practice evidence-based treatment. The paper goes on to explore the challenges in those areas, with particular reference to treatment engagement and barriers to care, as well as treatment non-response. The final section addresses innovative solutions to these challenges through improvements in agreed terminology and definitions, strategies to increase engagement, early identification approaches, understanding predictors of treatment outcome, and innovations in treatment. Treatment innovations include enhancing existing treatments, emerging non-trauma-focused interventions, novel pharmacotherapy, personalized medicine approaches, advancing functional outcomes, family intervention and support, and attention to physical health.

Dendritic Cells Cross-Present Immunogenic Lentivector-Encoded Antigen from Transduced Cells to Prime Functional T Cell Immunity.

Recombinant lentiviral vectors (LVs) are highly effective vaccination vehicles that elicit protective T cell immunity in disease models. Dendritic cells (DCs) acquire antigen at sites of vaccination and migrate to draining lymph nodes, where they prime vaccine-specific T cells. The potency with which LVs activate CD8+ T cell immunity has been attributed to the transduction of DCs at the immunization site and durable presentation of LV-encoded antigens. However, it is not known how LV-encoded antigens continue to be presented to T cells once directly transduced DCs have turned over. Here, we report that LV-encoded antigen is efficiently cross-presented by DCs in vitro. We have further exploited the temporal depletion of DCs in the murine CD11c.DTR (diphtheria toxin receptor) model to demonstrate that repopulating DCs that were absent at the time of immunization cross-present LV-encoded antigen to T cells in vivo. Indirect presentation of antigen from transduced cells by DCs is sufficient to prime functional effector T cells that control tumor growth. These data suggest that DCs cross-present immunogenic antigen from LV-transduced cells, thereby facilitating prolonged activation of T cells in the absence of circulating LV particles. These are findings that may impact on the future design of LV vaccination strategies.

Depletion of CD11c⁺ cells in the CD11c.DTR model drives expansion of unique CD64⁺ Ly6C⁺ monocytes that are poised to release TNF-α.

Dendritic cells (DCs) play a vital role in innate and adaptive immunities. Inducible depletion of CD11c(+) DCs engineered to express a high-affinity diphtheria toxin receptor has been a powerful tool to dissect DC function in vivo. However, despite reports showing that loss of DCs induces transient monocytosis, the monocyte population that emerges and the potential impact of monocytes on studies of DC function have not been investigated. We found that depletion of CD11c(+) cells from CD11c.DTR mice induced the expansion of a variant CD64(+) Ly6C(+) monocyte population in the spleen and blood that was distinct from conventional monocytes. Expansion of CD64(+) Ly6C(+) monocytes was independent of mobilization from the BM via CCR2 but required the cytokine, G-CSF. Indeed, this population was also expanded upon exposure to exogenous G-CSF in the absence of DC depletion. CD64(+) Ly6C(+) monocytes were characterized by upregulation of innate signaling apparatus despite the absence of inflammation, and an increased capacity to produce TNF-α following LPS stimulation. Thus, depletion of CD11c(+) cells induces expansion of a unique CD64(+) Ly6C(+) monocyte population poised to synthesize TNF-α. This finding will require consideration in experiments using depletion strategies to test the role of CD11c(+) DCs in immunity.

OX40- and CD27-mediated costimulation synergizes with anti-PD-L1 blockade by forcing exhausted CD8+ T cells to exit quiescence.

Exhaustion of chronically stimulated CD8(+) T cells is a significant obstacle to immune control of chronic infections or tumors. Although coinhibitory checkpoint blockade with anti-programmed death ligand 1 (PD-L1) Ab can restore functions to exhausted T cell populations, recovery is often incomplete and dependent upon the pool size of a quiescent T-bet(high) subset that expresses lower levels of PD-1. In a model in which unhelped, HY-specific CD8(+) T cells gradually lose function following transfer to male bone marrow transplantation recipients, we have explored the effect of shifting the balance away from coinhibition and toward costimulation by combining anti-PD-L1 with agonistic Abs to the TNFR superfamily members, OX40 and CD27. Several weeks following T cell transfer, both agonistic Abs, but especially anti-CD27, demonstrated synergy with anti-PD-L1 by enhancing CD8(+) T cell proliferation and effector cytokine generation. Anti-CD27 and anti-PD-L1 synergized by downregulating the expression of multiple quiescence-related genes concomitant with a reduced frequency of T-bet(high) cells within the exhausted population. However, in the presence of persistent Ag, the CD8(+) T cell response was not sustained and the overall size of the effector cytokine-producing pool eventually contracted to levels below that of controls. Thus, CD27-mediated costimulation can synergize with coinhibitory checkpoint blockade to switch off molecular programs for quiescence in exhausted T cell populations, but at the expense of losing precursor cells required to maintain a response.

The silencing effects of the childhood innocence ideal: the perceptions and practices of fathers in educating their children about sexuality.

This study employed Interpretative Phenomenological Analysis to explore eight fathers' perceptions and practices in talking to their ten year old children about puberty, relationships and reproduction. The fathers participated in face to face interviews which were analysed idiographically initially, followed by analysis at the group level. Interpretations were then developed through critical application of a Foucauldian lens of governmentality and biopower. The results revealed a tension between the fathers' cognitions, accounts and behaviours. Their practices were largely characterised by silence yet they reported positive attitudes towards children's sexuality education and perceived themselves as equipped and willing to take on the role of sexuality educator. They also reported enjoying open relationships with their children. Interpretations centred on contradictions and conflict between the majority of the fathers' aspirations and the compelling nature of the childhood innocence discourse as a technology of governmentality. Whilst all of the fathers felt that it was in their children's interests to learn about sexuality, all but one adhered to hegemonic protective discourses and unquestioningly integrated their normalising effects into their fathering practices which, it is argued, may paradoxically render their children more vulnerable both now and in the future.

Cell-intrinsic regulation of murine dendritic cell function and survival by prereceptor amplification of glucocorticoid.

Although the inhibitory effects of therapeutic glucocorticoids (GCs) on dendritic cells (DCs) are well established, the roles of endogenous GCs in DC homeostasis are less clear. A critical element regulating endogenous GC concentrations involves local conversion of inactive substrates to active 11-hydroxyglucocorticoids, a reduction reaction catalyzed within the endoplasmic reticulum by an enzyme complex containing 11ß-hydroxysteroid dehydrogenase type 1 (11ßHSD1) and hexose-6-phosphate dehydrogenase (H6PDH). In this study, we found that this GC amplification pathway operates both constitutively and maximally in steady state murine DC populations and is unaffected by additional inflammatory stimuli. Under physiologic conditions, 11ßHSD1-H6PDH increases the sensitivity of plasmacytoid DCs (pDCs) to GC-induced apoptosis and restricts the survival of this population through a cell-intrinsic mechanism. Upon CpG activation, the effects of enzyme activity are overridden, with pDCs becoming resistant to GCs and fully competent to release type I interferon. CD8α(+) DCs are also highly proficient in amplifying GC levels, leading to impaired maturation following toll-like receptor-mediated signaling. Indeed, pharmacologic inhibition of 11ßHSD1 synergized with CpG to enhance specific T-cell responses following vaccination targeted to CD8α(+) DCs. In conclusion, amplification of endogenous GCs is a critical cell-autonomous mechanism for regulating the survival and functions of DCs in vivo.

Dendritic cells in tissues: in situ stimulation of immunity and immunopathology.

Dendritic cells (DCs) prime and orchestrate naïve T cell immunity in lymphoid organs, but recent data also highlight the importance of DC-effector T cell interactions in tissues. These studies suggest that effector T cells require a second activating step in situ from tissue DCs to become fully competent for effector functions and/or proliferation and survival. DC stimulation of effector T cells within tissues has evolved as a mechanism to ensure that T cells are activated to their full potential only at the site of ongoing infection. Here, we propose that under conditions of uncontrolled inflammation and release of tissue antigens, the same DC-dependent checkpoint perpetuates a destructive response and immunopathology.

Cancer vaccines: from an immunology perspective.

The concept of a therapeutic cancer vaccine to activate anti-tumour immunity pre-dates innovations in checkpoint blockade immunotherapies. However, vaccination strategies have yet to show the hoped-for successes in patients, and unanswered questions regarding the underlying immunological mechanisms behind cancer vaccines have hampered translation to clinical practice. Recent advances in our understanding of the potential of tumour mutational burden and neo-antigen-reactive T cells for response to immunotherapy have re-ignited enthusiasm for cancer vaccination strategies, coupled with the development of novel mRNA-based vaccines following successes in prevention of COVID-19. Here we summarise current developments in cancer vaccines and discuss how advances in our comprehension of the cellular interplay in immunotherapy-responsive tumours may inform better design of therapeutic cancer vaccines, with a focus on the role of dendritic cells as the orchestrators of anti-tumour immunity. The increasing number of clinical trials and research being funnelled into cancer vaccines has demonstrated the 'proof-of-principle', supporting the hypothesis that therapeutic vaccines have potential as an immuno-oncology agent. For efficacious and safe cancer vaccines to be developed, better understanding of the underpinning immunological mechanisms is paramount.