A novel cellular pathway of antigen presentation and CD4 T cell activation in vivo

Dendritic cell activation of CD4 T cells in the lymph node draining a site of infection or vaccination is widely considered the central event in initiating adaptive immunity. The accepted dogma is that this occurs by stimulating local activation and antigen acquisition by dendritic cells, with subsequent lymph node migration, however the generalizability of this mechanism is unclear. Here we show that in some circumstances antigen can bypass the injection site inflammatory response, draining freely and rapidly to the lymph nodes where it interacts with subcapsular sinus (SCS) macrophages resulting in their death. Debris from these dying SCS macrophages is internalized by monocytes recruited from the circulation. This coordinated response leads to antigen presentation by monocytes and interactions with naïve CD4 T cells that can drive the initiation of T cell and B cell responses. These studies demonstrate an entirely novel pathway leading to initiation of adaptive immune responses in vivo

Nurses and midwives' experiences with a peer group clinical supervision intervention: A pilot study

Aim: This study aimed to evaluate differences in supervisees' understanding of clinical supervision and their perceptions of organisational functioning before and after engaging in peer-group clinical supervision. Background: Protected reflective time allows discussion of complex issues affecting health care. Peer-group clinical supervision is one model of clinical supervision that could facilitate this, but it is poorly understood. Methods: A preâ post intervention pilot study was performed. The intervention was delivered over a 12-month period. Data were collected using surveys on demographic and work-related factors and experience of clinical supervision pre- and post intervention. Results: Adaptability increased significantly between the pre- and post surveys. The post survey data showed finding time for clinical supervision scoring lowest with open-ended comments reinforcing this. The supervisees found the sessions to offer a safe place despite initial concerns. Conclusion: The peer-group model of clinical supervision allowed supervisees to build a rapport and trust with their colleagues and share experiences. Implications for Nursing Management: The benefits to participating in peer-group clinical supervision traversed the individual and organisation. These data support the implementation of such sessions while addressing workload and time pressures to aid participation

Peer group clinical supervision: Qualitative perspectives from nurse supervisees, managers, and supervisors

Background: Clinical supervision helps promote practitioners' personal and professional development through fostering a supportive relationship and working alliance. Peer group clinical supervision is a form of clinical supervision whereby two or more nurses engage in a supervision process to improve their professional practice and provide quality care. Aim: To explore the experiences of supervision from the perspectives of nurse supervisees, their direct line managers, and clinical supervisors. Methods: A qualitative descriptive pragmatic design was used. Individual interviews and focus groups were conducted with 27 participants. Data were analysed using deductive content analysis. Findings: Three main categories were identified: Perceived benefits of peer group clinical supervision, challenges faced during peer group clinical supervision, and enhancements for future peer group clinical supervision sessions. Stress reduction, problem solving, managing change, and improved prioritisation were amongst the benefits gained from clinical supervision. Challenges included competing work demands, staffing issues, and the duration, location, and process of supervision. Participants recommended adding time to the allocated supervision hour, raising awareness of peer group clinical supervision in advance, and training expert supervisors. Discussion: The space for peer group clinical supervision needs to be primed beforehand through providing and ensuring protected time, the availability of experienced supervisors, and raising key stakeholders' awareness of what supervision entails. Stress caused by competing work demands and the fear of losing momentum need to be considered by services in advance. Conclusion: Findings support the planning, delivery, and evaluation of future peer group clinical supervision sessions, while addressing challenges identified by study participants

Modules, networks and systems medicine for understanding disease and aiding diagnosis

Many common diseases, such as asthma, diabetes or obesity, involve altered interactions between thousands of genes. High-throughput techniques (omics) allow identification of such genes and their products, but functional understanding is a formidable challenge. Network-based analyses of omics data have identified modules of disease-associated genes that have been used to obtain both a systems level and a molecular understanding of disease mechanisms. For example, in allergy a module was used to find a novel candidate gene that was validated by functional and clinical studies. Such analyses play important roles in systems medicine. This is an emerging discipline that aims to gain a translational understanding of the complex mechanisms underlying common diseases. In this review, we will explain and provide examples of how network-based analyses of omics data, in combination with functional and clinical studies, are aiding our understanding of disease, as well as helping to prioritize diagnostic markers or therapeutic candidate genes. Such analyses involve significant problems and limitations, which will be discussed. We also highlight the steps needed for clinical implementation

A comparison in a youth population between those with and without a history of concussion using biomechanical reconstruction

OBJECTIVE: Concussion is a common topic of research as a result of the short- and long-term effects it can have on the affected individual. Of particular interest is whether previous concussions can lead to a biomechanical susceptibility, or vulnerability, to incurring further head injuries, particularly for youth populations. The purpose of this research was to compare the impact biomechanics of a concussive event in terms of acceleration and brain strains of 2 groups of youths: those who had incurred a previous concussion and those who had not. It was hypothesized that the youths with a history of concussion would have lower-magnitude biomechanical impact measures than those who had never suffered a previous concussion. METHODS: Youths who had suffered a concussion were recruited from emergency departments across Canada. This pool of patients was then separated into 2 categories based on their history of concussion: those who had incurred 1 or more previous concussions, and those who had never suffered a concussion. The impact event that resulted in the brain injury was reconstructed biomechanically using computational, physical, and finite element modeling techniques. The output of the events was measured in biomechanical parameters such as energy, force, acceleration, and brain tissue strain to determine if those patients who had a previous concussion sustained a brain injury at lower magnitudes than those who had no previously reported concussion. RESULTS: The results demonstrated that there was no biomechanical variable that could distinguish between the concussion groups with a history of concussion versus no history of concussion. CONCLUSIONS: The results suggest that there is no measureable biomechanical vulnerability to head impact related to a history of concussions in this youth population. This may be a reflection of the long time between the previous concussion and the one reconstructed in the laboratory, where such a long period has been associated with recovery from injury

Clinical risk score for persistent postconcussion symptomsamong children with acute concussion in the ED

IMPORTANCE Approximately one-third of children experiencing acute concussion experience ongoing somatic, cognitive, and psychological or behavioral symptoms, referred to as persistent postconcussion symptoms (PPCS). However, validated and pragmatic tools enabling clinicians to identify patients at risk for PPCS do not exist. OBJECTIVE To derive and validate a clinical risk score for PPCS among children presenting to the emergency department. DESIGN, SETTING, AND PARTICIPANTS Prospective, multicenter cohort study (Predicting and Preventing Postconcussive Problems in Pediatrics [5P]) enrolled young patients (aged 5-\u3c18 years) who presented within 48 hours of an acute head injury at 1 of 9 pediatric emergency departments within the Pediatric Emergency Research Canada (PERC) network from August 2013 through September 2014 (derivation cohort) and from October 2014 through June 2015 (validation cohort). Participants completed follow-up 28 days after the injury. EXPOSURES All eligible patients had concussions consistent with the Zurich consensus diagnostic criteria. MAIN OUTCOMES AND MEASURES The primary outcomewas PPCS risk score at 28 days, which was defined as 3 or more new or worsening symptoms using the patient-reported Postconcussion Symptom Inventory compared with recalled state of being prior to the injury. RESULTS In total, 3063 patients (median age, 12.0 years [interquartile range, 9.2-14.6 years]; 1205 [39.3%] girls) were enrolled (n = 2006 in the derivation cohort; n = 1057 in the validation cohort) and 2584 of whom (n = 1701 [85%] in the derivation cohort; n = 883 [84%] in the validation cohort) completed follow-up at 28 days after the injury. Persistent postconcussion symptoms were present in 801 patients (31.0%) (n = 510 [30.0%] in the derivation cohort and n = 291 [33.0%] in the validation cohort). The 12-point PPCS risk score model for the derivation cohort included the variables of female sex, age of 13 years or older, physician-diagnosed migraine history, prior concussion with symptoms lasting longer than 1 week, headache, sensitivity to noise, fatigue, answering questions slowly, and 4 or more errors on the Balance Error Scoring System tandem stance. The area under the curve was 0.71 (95%CI, 0.69-0.74) for the derivation cohort and 0.68 (95%CI, 0.65-0.72) for the validation cohort. CONCLUSIONS AND RELEVANCE A clinical risk score developed among children presenting to the emergency department with concussion and head injury within the previous 48 hours had modest discrimination to stratify PPCS risk at 28 days. Before this score is adopted in clinical practice, further research is needed for external validation, assessment of accuracy in an office setting, and determination of clinical utility

Future business and the role of purchasing and supply management:Opportunities for ‘business-not-as-usual’ PSM research

The raison d'être for this article is simple: traditional ways of researching, theorizing, and practicing purchasing and supply management (PSM) are no longer sufficient to ‘meet the moment’. Scholars need to advance a “business-not-as-usual” footing approach to their work, if they are to make a meaningful contribution to addressing the current and future emergencies, as highlighted by recent extreme weather and the COVID-19 pandemic. Yet, what can this, or should this, mean for a field rooted in traditional business thinking? This article builds on the Journal of Purchasing and Supply Management's (JPSM) 25th Anniversary Special Issue editorial (2019); members of the JPSM's editorial team advance their unique perspectives on what “business-not-as-usual” means for PSM. Specifically, we advocate both thinking much more widely, in scope and ambition, than we currently do, and simultaneously building our ability to comprehend supply chains in a more nuanced and granular way. We explore whether the bias toward positivist work has omitted potentially interesting findings, and viewpoints. This leads to a call to re-think how we approach our work: should the key criteria always be to focus on theory development or testing? Should academics “think bigger”? Turning to specific research themes, illustrations of how our current thinking can be challenged or broadened by addressing the circular economy, and role of purchasing and innovation. Specifically, the focus on the PSM function as an intrapreneur within the larger organization, and the role of innovation and technology in PSM work. Taken together, we hope the ideas and arguments presented here will inform and inspire ambitious and novel approaches to PSM research with significant and enduring impact on the transformation of business